1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota; and 2Department of Biomedical Engineering, University of California, Davis, California
Submitted 8 December 2004 ; accepted in final form 16 March 2005
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
membrane domains; adhesion; leukocyte; inflammation
Neutrophils that have accumulated within the microvasculature capture free-flowing leukocytes (13, 69). This process of indirect leukocyte tethering accelerates neutrophil accumulation and is facilitated by L-selectin (2, 4, 74, 85). Consistent with its role in amplifying the extent and rate of neutrophil accumulation, L-selectin is tightly regulated, which involves rapid and transient increases in its binding activity (26, 70). C-type lectins achieve high-affinity binding through the presentation of multiple carbohydrate recognition domains in a single polypeptide or by clustering (reviewed in Ref. 86). L-selectin, which contains a single carbohydrate recognition domain, undergoes clustering on neutrophil stimulation (21). Considering that all physiological ligands of L-selectin present multiple low-affinity oligosaccharide binding sites, inducible L-selectin clustering would likely provide a highly efficient means of regulating its binding activity. Indeed, L-selectin when clustered greatly enhances leukocyte tethering (12, 48). This process also results in signaling and the induction of various postadhesion events, including oxidative burst, degranulation, cytokine expression, actin polymerization, and CD18 integrin activation (9, 21, 22, 30, 43, 64, 67, 71, 76, 80, 81).
Lateral heterogeneity of lipids and proteins occurs in the plasma membrane of neutrophils on their stimulation. This process results in the formation of membrane domains within the surrounding bilayer that are organized by interactions between cholesterol-enriched lipids and by the association of particular transmembrane proteins with the actin cytoskeleton (54, 55, 62). Such components progress from a uniform distribution in the plasma membrane to small patches and eventually to segregated caps at the uropod and lamellipodium of polarized neutrophils (55, 62), which has been observed with living cells (17, 38). Leukocyte membrane domains are identified by various approaches, including detergent resistance, lipid fluidity indicators, and resident glycosyl phosphatidylinositol (GPI)-anchored proteins (17, 20, 38, 42, 46, 51, 55, 58, 62). In this study, we examined L-selectin partitioning in the plasma membrane of neutrophils on inducible clustering and the role of cytoskeletal interactions in regulating its mobility.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Cells.
Venous blood was collected in sodium heparin from normal, healthy donors upon informed consent. These procedures were performed in accordance with protocols approved by the Institutional Review Board: Human Subjects Committee at the Universities of Minnesota and California, Davis. Total leukocytes and red blood cells were isolated by dextran sedimentation, and neutrophils were isolated by an additional Ficoll-Hypaque centrifugation, as previously described (74, 83, 85). Transduced K562 cells (erythroblast) expressing human wild-type L-selectin, 8-residue-truncated (8) L-selectin, or 16-residue-truncated (
16) L-selectin (see Fig. 3) were maintained in modified RPMI 1640 medium as previously described (52).
|
Immunofluorescence microscopy. Analysis of the colocalization of L-selectin with other cell surface determinants after neutrophil stimulation with E-selectin/Fc was performed as previously described (21, 22). Briefly, neutrophils (1 x 106/ml) were preincubated in the presence or absence of 100 nM E-selectin/Fc and labeled with anti-L-selectin-PE and anti-CD55-FITC or anti-CD11c-FITC for 10 min at 23°C. The reaction was stopped by the addition of 100 ml of 2% paraformaldehyde in PBS and allowed to fix for 30 min at 4°C. After fixation, excess MAbs were removed by centrifugation, and the resulting neutrophil suspension was sealed between a coverslip and a slide for fluorescent imaging. No difference in binding was observed between neutrophil suspensions labeled before and after fixation. Labeled cells were imaged by fluorescence microscopy with a Nikon TE2000-S inverted microscope and a x60 Plan Apo objective (numerical aperture = 1.4) under oil and a Sutter filter wheel (Sutter Instrument, Novato, CA) housing excitation filters appropriate for FITC and PE fluorophores. Images were captured with an ORCA digital charge-coupled device camera (Hamamatsu Photonics, Hamamatsu City, Japan) and Simple PCI acquisition software (Compix, Cranberry Township, PA). For quantitation of receptor colocalization, a cluster was defined as a localized region of the membrane with pixel intensity at least threefold greater than background fluorescent intensity. Pixel intensity values are unitless and range from 0 to 255. A threshold intensity value over the cell membrane was assigned based on that of nonimmune fluorescent mouse IgG. This value typically ranges from 80 to 140, with clusters achieving a maximum intensity value of 255 by default. After thresholding on the background fluorescence, the percent colocalization was determined. Baseline colocalization is mathematically defined as the extent of coclustering predicted for a random distribution of membrane receptors. It is defined as the average percentage of membrane area occupied by green (CD55) pixels after image thresholding based on cluster definition. This area fraction defines the level of L-selectin-CD55 coclustering expected for a random distribution of CD55 fluorescence.
Analysis of the colocalization of L-selectin with other cell surface determinants on neutrophils after antibody-mediated cross-linking was performed as previously described (21, 22). Briefly, 3 x 106 neutrophils were stained on ice with a particular primary MAb that was then cross-linked with FITC-conjugated F(ab')2 goat anti-mouse IgG either on ice or at 37°C for 30 min, after which neutrophils were fixed in 2% paraformaldehyde and labeled with biotin-anti-CD55, biotin-anti-L-selectin, or biotin-anti-CD45, which was detected with streptavidin-Cy3. Fixation with paraformaldehyde was repeated. Cells were applied to poly-L-lysine-coated coverslips and mounted with Vectashield Hard-Set mounting medium (Vector Laboratories, Burlingame, CA). Analysis of fluorescence was performed on a Bio-Rad 1024 confocal laser-scanning microscope with a x60 oil immersion objective (numerical aperture = 1.4) (Bio-Rad Laboratories, Hercules, CA). Double-channel fluorescence was analyzed at 488-nm excitation and 522 ± 16-nm emission for FITC and 568-nm excitation and 605 ± 16-nm emission for Cy3. Cell staining was analyzed by scanning horizontal sections at 1-µm vertical steps. Images were recorded (512 x 512 pixels) and processed with Adobe Photoshop software (Mountain View, CA).
Other immunoassays. Flow cytometry, immunoprecipitation, SDS-PAGE, and immunoblotting were performed as previously described (1, 52, 74, 82, 84). For flow cytometry, antibody-labeled cells were analyzed (10,000 cells/sample) or sorted on a FACSCalibur instrument (Becton-Dickinson Immunocytometry Systems, San Jose, CA).
Discontinuous density gradient centrifugation.
Typically, 5 x 107 cells were washed in ice-cold TNE buffer (25 mM Tris-Cl, pH 7.4, 150 mM NaCl, and 5 mM EDTA) and then detergent lysed for 20 min with 2 ml of lysis buffer (1% Triton X-100 in TNE buffer containing Complete Protease Inhibitor Cocktail). After lysis, 2.5 ml of ice-cold TNE buffer containing 80% sucrose was thoroughly mixed with the lysate. This mixture was transferred to ultracentrifuge tubes and overlaid first with 6.5 ml of 35% sucrose in TNE buffer and then 0.8 ml of 5% sucrose in TNE buffer. The gradient was centrifuged for 17 h at 100,000 g in a Beckman L860M ultracentrifuge at 4°C (Beckman Coulter, Fullerton, CA). Fractions were recovered from the top, starting with the interface containing the detergent-resistant domain and then afterward in 1-ml increments.
Detergent-resistant membrane and actin cytoskeleton disruption.
MCD treatment was performed to deplete cholesterol from the detergent-resistant membrane. Typically 2 x 107 cells were washed twice in buffered saline solution (BSS; in mM: 20 HEPES, 135 NaCl, 5 KCl, 1.8 CaCl2, 1 MgCl2, and 5.6 glucose) and then resuspended at 4 x 106 cells/ml in BSS containing 10 mM M
CD and BSA (1 mg/ml). An additional 12.5 ml of RPMI containing 10 mM M
CD plus BSA was then added to the cells. Cells were incubated at 37°C for various time points, after which the cells were washed twice with BSS. Latrunculin A treatment was performed to block the polymerization of monomeric G-actin to F-actin (3, 8, 53, 87). Typically 3 x 106 cells were incubated with 2 µM latrunculin A in HBSS for 10 min at 37°C. Latrunculin A is a reversible inhibitor and thus was not removed before L-selectin or CD55 patching for confocal microscopy.
Facilitated L-selectin association with detergent-insoluble cytoskeleton. Typically, 1 x 107 cells were treated with DREG-55 MAb on ice for 30 min, washed with HBSS, and treated with F(ab')2 goat anti-mouse IgG on ice for 30 min. After washing, the cells were detergent extracted (1% Triton X-100 in HBSS containing 5 mM NaN3, 5 mM HEPES, and Complete Protease Inhibitor Cocktail) on ice for 1 h. Next either the lysate was centrifuged at 20,800 g for 15 min, with the resulting pellet, which contains the detergent-resistant membrane and detergent-insoluble cytoskeleton, solubilized in cytoskeletal pellet solubilization buffer (20 mM NaH2PO4, pH 7.0, 0.15 M NaCl, 2 mM EDTA, 2 mM PMSF, 1% Nonidet P-40, 1% sodium deoxycholate, and 0.1% SDS) for 1 h, or the lysate was subjected to density gradient centrifugation (see below) to separate the detergent-resistant membrane and detergent-insoluble cytoskeleton. The resulting cytoskeletal pellet was solubilized with cytoskeletal pellet solubilization buffer. In some cases, cells were initially cell surface biotinylated to label proteins in the plasma membrane. This was performed with EZ-Link sulfo-NHS-LC biotin.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Mobility and partitioning of L-selectin in plasma membrane are regulated by its association with actin cytoskeleton.
L-selectin has been reported by various groups to associate with the actin cytoskeleton (15, 27, 28, 45, 59). We assessed the effects of disrupting this association on the lateral mobility of L-selectin in the plasma membrane. In an initial series of experiments, the actin cytoskeleton of neutrophils was disrupted with latrunculin A, which blocks the polymerization of monomeric G-actin to F-actin (3, 8, 53, 87). We observed that L-selectins association with the actin cytoskeleton on antibody cross-linking was reduced by 44% after latrunculin A treatment, as determined by density gradient centrifugation and examination of the cytoskeletal pellet (data not shown). In the presence of latrunculin A, L-selectin coalesced into fewer and, on average, larger patches after antibody cross-linking (Fig. 2A). Image analysis of micrographs revealed that for sham-treated neutrophils (Fig. 2A1), the average number of L-selectin patches per cell and their average size were 13.48 ± 4.51 and 0.71 ± 0.32 µm, respectively, whereas for latrunculin A-treated neutrophils (Fig. 2A2) the average number of L-selectin patches per cell and their average size were 2.72 ± 1.46 and 3.04 ± 2.20 µm, respectively (means ± SD, n = 25 cells per treatment group). The number of patches per cell differed significantly between treatment groups (P < 0.001; data are representative of 3 separate experiments involving different blood donors). The large L-selectin patches occurring on latrunculin A-treated neutrophils also contained colocalized CD55 (Fig. 2A). Of interest is that antibody cross-linking of CD55 on latrunculin A-treated neutrophils resulted in patching and coclustering of L-selectin (Fig. 2B), which was not as apparent in the absence of latrunculin A (Fig. 1F). One explanation for this finding is that by disrupting L-selectins association with the actin cytoskeleton it was free to be "swept up" with CD55 on its patching. Alternatively, Leitinger and Hogg (46) reported a similar effect on leukocyte function-associated antigen-1 (LFA-1) after antibody-mediated patching of CD55 on human T cells treated with either cytochalasin D or latrunculin A and proposed that disrupting cytoskeletal anchorage by LFA-1 results in its lateral migration into microdomains occurring on resting cells.
|
|
To verify that 16 L-selectin partitioning in the low-density fractions was not an artifact or anomalous process on detergent extraction and fractionation, M
CD was used to disrupt cholesterol-enriched, detergent-resistant lipid complexes. M
CD forms stable complexes with cholesterol and is used to extract these molecules from the plasma membrane (29, 61, 63). We observed that M
CD treatment of K562 transductants reduced the level of Src kinases in the detergent-resistant domain (Fig. 4C). M
CD treatment, which had no effect on the cell surface expression levels of
16 L-selectin on resting cells, as determined by flow cytometry (data not shown), also reduced the levels of
16 L-selectin partitioning in the detergent-resistant membrane (Fig. 4C). Actin levels were equivalent in untreated and treated samples, indicating that equivalent amounts of detergent extracts were analyzed (Fig. 4C). In contrast to the mature form of
16 L-selectin, detection of its precursor increased after treatment of the transductants with M
CD (Fig. 4C), which perhaps was due to a more efficient extraction after cholesterol depletion. Together our data demonstrate that disrupting L-selectins association with the actin cytoskeleton, by either latrunculin A or cytoplasmic region deletion, increases its mobility and capacity to partition in membrane domains, suggesting that constitutive cytoskeletal interactions may normally impede L-selectin clustering.
Conserved cationic motif in cytoplasmic region of L-selectin is critical for membrane domain partitioning and function.
We next examined features of L-selectins cytoplasmic region that may be important for regulating its lateral migration in the plasma membrane. Of initial interest was a highly conserved cationic motif located proximal to the cell membrane (Fig. 3). We directly examined this segment of L-selectin by truncating the cytoplasmic region by eight residues (8 L-selectin; Fig. 3). To examine the plasma membrane partitioning of
8 L-selectin, transduced K562 cells were detergent extracted and subjected to density gradient centrifugation, as described above. Immunoblotting of the gradient fractions revealed
8 L-selectin partitioned in the high-density fractions (detergent-soluble membrane; Fig. 5A), as occurred with wild-type L-selectin (Fig. 4B). Moreover, antibody cross-linking resulted in the association of wild-type and
8 L-selectin with the detergent-insoluble cytoskeleton of extracted cells (Fig. 5B). These data indicate that wild-type and
8 L-selectin are similar in their membrane domain partitioning and capacity to associate with the actin cytoskeleton.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our studies involving expressed structural variants of L-selectin show that a conserved cationic motif in the cytoplasmic region of L-selectin, juxtaposed to the cell membrane (Fig. 3), is critical for regulating L-selectins mobility. For instance, 16 L-selectin did not associate with the actin cytoskeleton and partitioned in the detergent-resistant membrane, in contrast to
8 and wild-type L-selectin. These data are congruent with intermolecular interactions reported to take place within the conserved cationic element of L-selectins cytoplasmic region, including calmodulin and the ezrin-radixin-moesin proteins ezrin and moesin (27, 28, 32, 52). The latter molecules concentrate in microvilli projections, as does L-selectin (14), and link a subset of transmembrane proteins to the actin cytoskeleton (6). It is conceivable that one or more of these interactions with L-selectin may facilitate constitutive restraint by the cytoskeleton. Whether this is disrupted in an inducible manner during neutrophil stimulation to enhance L-selectin mobility and clustering has yet to be resolved. Incidentally, L-selectin is phosphorylated at serine residues juxtaposed to the conserved motif on neutrophil stimulation, and this correlates in time with transient increases in L-selectin binding activity and subsequent transmembrane signal transduction (22, 26, 35). It will be useful to determine whether this event promotes a transient release of L-selectin from cytoskeletal restraint, thus increasing the efficiency and kinetics of inducible L-selectin clustering.
Despite the increased mobility and clustering of L-selectin that occurs by molecules devoid of a cytoplasmic region or on disrupting actin microfilaments, these manipulations abrogate L-selectin-dependent cell tethering under shear flow conditions (Fig. 6; Refs. 11, 33). This suggests that an association with the actin cytoskeleton is also necessary to stabilize L-selectin. Thus L-selectins interactions with the actin cytoskeleton may occur in a dynamic manner that provides negative and positive regulation. In resting neutrophils, constitutive cytoskeletal interactions may confine L-selectin to prevent clustering and consequently reduce adhesiveness and signaling. After neutrophil stimulation, induced cytoskeletal anchorage may stabilize L-selectin and promote its effector functions. Consistent with the latter are studies by Ivetic et al. (27) showing that moesin interacts with L-selectin in an inducible manner. Moreover, current published data provide several examples of temporal and dynamic associations between various adhesion proteins and the actin cytoskeleton resulting in augmented function, including CD43, LFA-1, Mac-1, VCAM-1, and ICAM-1 (5, 10, 37, 46, 49, 73).
In closing, L-selectin clustering in membrane domains may not only bolster L-selectin function but also result in an adhesion complex. We have observed (21, 22) the coclustering of L-selectin, PSGL-1, and high-affinity Mac-1 on neutrophil stimulation. Hence, as neutrophils progress from accumulation to transmigration, the development of transient adhesion complexes, with various components collected together in a membrane domain, may provide proximity between receptors and signaling factors to facilitate efficient cell tethering and firm adhesion. Moreover, as it has recently been reported that E-selectin also localizes in membrane domains on endothelial cells (34), the coordination of the multistep process of leukocyte recruitment and transmigration may occur in a bidirectional manner within adhesion complexes.
![]() |
GRANTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Alon R, Fuhlbrigge RC, Finger EB, and Springer TA. Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow. J Cell Biol 135: 849865, 1996.[Abstract]
3. Ayscough KR, Stryker J, Pokala N, Sanders M, Crews P, and Drubin DG. High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A. J Cell Biol 137: 399416, 1997.
4. Bargatze RF, Kurk S, Butcher EC, and Jutila MA. Neutrophils roll on adherent neutrophils bound to cytokine-induced endothelial cells via L-selectin on the rolling cells. J Exp Med 180: 17851792, 1994.
5. Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, and Sanchez-Madrid F. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157: 12331245, 2002.
6. Bretscher A, Reczek D, and Berryman M. Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci 110: 30113018, 1997.
7. Brown DA and Rose JK. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68: 533544, 1992.[CrossRef][ISI][Medline]
8. Coue M, Brenner SL, Spector I, and Korn ED. Inhibition of actin polymerization by latrunculin A. FEBS Lett 213: 316318, 1987.[CrossRef][ISI][Medline]
9. Crockett-Torabi E, Sulenbarger B, Smith CW, and Fantone JC. Activation of human neutrophils through L-selectin and Mac-1 molecules. J Immunol 154: 22912302, 1995.
10. Delon J, Kaibuchi K, and Germain RN. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Immunity 15: 691701, 2001.[CrossRef][ISI][Medline]
11. Dwir O, Kansas GS, and Alon R. Cytoplasmic anchorage of L-selectin controls leukocyte capture and rolling by increasing the mechanical stability of the selectin tether. J Cell Biol 155: 145156, 2001.
12. Dwir O, Steeber DA, Schwarz US, Camphausen RT, Kansas GS, Tedder TF, and Alon R. L-selectin dimerization enhances tether formation to properly spaced ligand. J Biol Chem 277: 2113021139, 2002.
13. Eriksson EE, Xie X, Werr J, Thoren P, and Lindbom L. Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo. J Exp Med 194: 205218, 2001.
14. Erlandsen SL, Hasslen SR, and Nelson RD. Detection and spatial distribution of the 2 integrin (Mac-1) and L-selectin (LECAM-1) adherence receptors on human neutrophils by high-resolution field emission SEM. J Histochem Cytochem 41: 327333, 1993.
15. Evans SS, Schleider DM, Bowman LA, Francis ML, Kansas GS, and Black JD. Dynamic association of L-selectin with the lymphocyte cytoskeletal matrix. J Immunol 162: 36153624, 1999.
16. Foster LJ, De Hoog CL, and Mann M. Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc Natl Acad Sci USA 100: 58135818, 2003.
17. Frasch SC, Henson PM, Nagaosa K, Fessler MB, Borregaard N, and Bratton DL. Phospholipid flip-flop and phospholipid scramblase 1 (PLSCR1) co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils. J Biol Chem 279: 1762517633, 2004.
18. Frenette PS and Wagner DD. Insights into selectin function from knockout mice. Thromb Haemost 78: 6064, 1997.[ISI][Medline]
19. Geppert TD and Lipsky PE. Association of various T cell-surface molecules with the cytoskeleton. Effect of cross-linking and activation. J Immunol 146: 32983305, 1991.
20. Gomez-Mouton C, Abad JL, Mira E, Lacalle RA, Gallardo E, Jimenez-Baranda S, Illa I, Bernad A, Manes S, and Martinez AC. Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization. Proc Natl Acad Sci USA 98: 96429647, 2001.
21. Green CE, Pearson DN, Camphausen RT, Staunton DE, and Simon SI. Shear-dependent capping of L-selectin and P-selectin glycoprotein ligand 1 by E-selectin signals activation of high-avidity 2-integrin on neutrophils. J Immunol 172: 77807790, 2004.
22. Green CE, Pearson DN, Christensen NB, and Simon SI. Topographic requirements and dynamics of signaling via L-selectin on neutrophils. Am J Physiol Cell Physiol 284: C705C717, 2003.
23. Guyer DA, Moore KL, Lynam E, McEver RP, and Sklar LA. P-selectin glycoprotein ligand (PSGL-1) is a ligand for L-selectin in neutrophil aggregation. Blood 88: 24152421, 1996.
24. Hafezi-Moghadam A and Ley K. Relevance of L-selectin shedding for leukocyte rolling in vivo. J Exp Med 189: 939947, 1999.
25. Hafezi-Moghadam A, Thomas KL, Prorock AJ, Huo Y, and Ley K. L-selectin shedding regulates leukocyte recruitment. J Exp Med 193: 863872, 2001.
26. Haribabu B, Steeber DA, Ali H, Richardson RM, Snyderman R, and Tedder TF. Chemoattractant receptor-induced phosphorylation of L-selectin. J Biol Chem 272: 1396113965, 1997.
27. Ivetic A, Deka J, Ridley A, and Ager A. The cytoplasmic tail of L-selectin interacts with members of the Ezrin-Radixin-Moesin (ERM) family of proteins: cell activation-dependent binding of Moesin but not Ezrin. J Biol Chem 277: 23212329, 2002.
28. Ivetic A, Florey O, Deka J, Haskard DO, Ager A, and Ridley AJ. Mutagenesis of the ezrin-radixin-moesin binding domain of L-selectin tail affects shedding, microvillar positioning, and leukocyte tethering. J Biol Chem 279: 3326333272, 2004.
29. Janes PW, Ley SC, and Magee AI. Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. J Cell Biol 147: 447461, 1999.
30. Junge S, Brenner B, Lepple-Wienhues A, Nilius B, Lang F, Linderkamp O, and Gulbins E. Intracellular mechanisms of L-selectin induced capping. Cell Signal 11: 301308, 1999.[CrossRef][ISI][Medline]
31. Kahn J, Ingraham RH, Shirley F, Migaki GI, and Kishimoto TK. Membrane proximal cleavage of L-selectin: identification of the cleavage site and a 6-kD transmembrane peptide fragment of L-selectin. J Cell Biol 125: 461470, 1994.[Abstract]
32. Kahn J, Walcheck B, Migaki GI, Jutila MA, and Kishimoto TK. Calmodulin regulates L-selectin adhesion molecule expression and function through a protease-dependent mechanism. Cell 92: 809818, 1998.[CrossRef][ISI][Medline]
33. Kansas GS, Ley K, Munro JM, and Tedder TF. Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin. J Exp Med 177: 833838, 1993.
34. Kiely JM, Hu Y, Garcia-Cardena G, and Gimbrone MA Jr. Lipid raft localization of cell surface E-selectin is required for ligation-induced activation of phospholipase C. J Immunol 171: 32163224, 2003.
35. Kilian K, Dernedde J, Mueller EC, Bahr I, and Tauber R. The interaction of protein kinase C isozymes ,
, and
with the cytoplasmic domain of L-selectin is modulated by phosphorylation of the receptor. J Biol Chem 279: 3447234480, 2004.
36. Kindzelskii AL, Eszes MM, Todd RF III, and Petty HR. Proximity oscillations of complement type 4 (alphaX beta2) and urokinase receptors on migrating neutrophils. Biophys J 73: 17771784, 1997.[Abstract]
37. Kindzelskii AL, Laska ZO, Todd RF III, and Petty HR. Urokinase-type plasminogen activator receptor reversibly dissociates from complement receptor type 3 (alphaM beta2' CD11b/CD18) during neutrophil polarization. J Immunol 156: 297309, 1996.[Abstract]
38. Kindzelskii AL, Sitrin RG, and Petty HR. Cutting edge: Optical microspectrophotometry supports the existence of gel phase lipid rafts at the lamellipodium of neutrophils: apparent role in calcium signaling. J Immunol 172: 46814685, 2004.
39. Kishimoto TK, Jutila MA, and Butcher EC. Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci USA 87: 22442248, 1990.
40. Kishimoto TK, Walcheck B, and Rothlein R. Leukocyte adhesion, trafficking, and migration. In: Graft-vs-Host Disease (2nd ed.), edited by Ferrara JLM, Deeg HJ, and Burakoff SJ. New York: Dekker, 1997, p. 151178.
41. Krieglstein CF and Granger DN. Adhesion molecules and their role in vascular disease. Am J Hypertens 14: 44S54S, 2001.[CrossRef][ISI][Medline]
42. Kwiatkowska K and Sobota A. The clustered Fc receptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner. Eur J Immunol 31: 989998, 2001.[CrossRef][ISI][Medline]
43. Laudanna C, Constantin G, Baron P, Scarpini E, Scarlato G, Cabrini G, Dechecchi C, Rossi F, Cassatella MA, and Berton G. Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule. J Biol Chem 269: 40214026, 1994.
44. Leid JG and Jutila MA. Impact of polyunsaturated fatty acids on cytoskeletal linkage of L-selectin. Cell Immunol 228: 9198, 2004.[CrossRef][ISI][Medline]
45. Leid JG, Steeber DA, Tedder TF, and Jutila MA. Antibody binding to a conformation-dependent epitope induces L-selectin association with the detergent-resistant cytoskeleton. J Immunol 166: 48994907, 2001.
46. Leitinger B and Hogg N. The involvement of lipid rafts in the regulation of integrin function. J Cell Sci 115: 963972, 2002.
47. Leppanen A, Yago T, Otto VI, McEver RP, and Cummings RD. Model glycosulfopeptides from P-selectin glycoprotein ligand-1 require tyrosine sulfation and a core 2-branched O-glycan to bind to L-selectin. J Biol Chem 278: 2639126400, 2003.
48. Li X, Steeber DA, Tang ML, Farrar MA, Perlmutter RM, and Tedder TF. Regulation of L-selectin-mediated rolling through receptor dimerization. J Exp Med 188: 13851390, 1998.
49. Lub M, van Kooyk Y, van Vliet SJ, and Figdor CG. Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1. Mol Biol Cell 8: 341351, 1997.[Abstract]
50. Magee T, Pirinen N, Adler J, Pagakis SN, and Parmryd I. Lipid rafts: cell surface platforms for T cell signaling. Biol Res 35: 127131, 2002.[ISI][Medline]
51. Manes S, Mira E, Gomez-Mouton C, Lacalle RA, Keller P, Labrador JP, and Martinez AC. Membrane raft microdomains mediate front-rear polarity in migrating cells. EMBO J 18: 62116220, 1999.
52. Matala E, Alexander SR, Kishimoto TK, and Walcheck B. The cytoplasmic domain of L-selectin participates in regulating L-selectin endoproteolysis. J Immunol 167: 16171623, 2001.
53. Morton WM, Ayscough KR, and McLaughlin PJ. Latrunculin alters the actin-monomer subunit interface to prevent polymerization. Nat Cell Biol 2: 376378, 2000.[CrossRef][ISI][Medline]
54. Mukherjee S and Maxfield FR. Membrane domains. Annu Rev Cell Dev Biol 20: 839866, 2004.[CrossRef][ISI][Medline]
55. Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, and Luna EJ. Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem 277: 4339943409, 2002.
56. Osborn M and Weber K. The detergent-resistant cytoskeleton of tissue culture cells includes the nucleus and the microfilament bundles. Exp Cell Res 106: 339349, 1977.[CrossRef][ISI][Medline]
57. Painter RG, Gaarde W, and Ginsberg MH. Direct evidence for the interaction of platelet surface membrane proteins GPIIb and III with cytoskeletal components: protein crosslinking studies. J Cell Biochem 27: 186200, 1985.
58. Parolini I, Sargiacomo M, Lisanti MP, and Peschle C. Signal transduction and glycophosphatidylinositol-linked proteins (lyn, lck, CD4, CD45, G proteins, and CD55) selectively localize in Triton-insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes. Blood 87: 37833794, 1996.
59. Pavalko FM, Walker DM, Graham L, Goheen M, Doerschuk CM, and Kansas GS. The cytoplasmic domain of L-selectin interacts with cytoskeletal proteins via alpha-actinin: receptor positioning in microvilli does not require interaction with alpha-actinin. J Cell Biol 129: 11551164, 1995.[Abstract]
60. Rodgers W and Rose JK. Exclusion of CD45 inhibits activity of p56lck associated with glycolipid-enriched membrane domains. J Cell Biol 135: 15151523, 1996.[Abstract]
61. Scheiffele P, Roth MG, and Simons K. Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain. EMBO J 16: 55015508, 1997.
62. Seveau S, Eddy RJ, Maxfield FR, and Pierini LM. Cytoskeleton-dependent membrane domain segregation during neutrophil polarization. Mol Biol Cell 12: 35503562, 2001.
63. Sheets ED, Holowka D, and Baird B. Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcRI and their association with detergent-resistant membranes. J Cell Biol 145: 877887, 1999.
64. Simon SI, Burns AR, Taylor AD, Gopalan PK, Lynam EB, Sklar LA, and Smith CW. L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) 2-integrin. J Immunol 155: 15021514, 1995.[Abstract]
65. Simons K and Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1: 3139, 2000.[CrossRef][ISI][Medline]
66. Sitrin RG, Johnson DR, Pan PM, Harsh DM, Huang J, Petty HR, and Blackwood RA. Lipid raft compartmentalization of urokinase receptor signaling in human neutrophils. Am J Respir Cell Mol Biol 30: 233241, 2004.
67. Smolen JE, Petersen TK, Koch C, OKeefe SJ, Hanlon WA, Seo S, Pearson D, Fossett MC, and Simon SI. L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase. J Biol Chem 275: 1587615884, 2000.
68. Snapp KR, Wagers AJ, Craig R, Stoolman LM, and Kansas GS. P-selectin glycoprotein ligand-1 is essential for adhesion to P-selectin but not E-selectin in stably transfected hematopoietic cell lines. Blood 89: 896901, 1997.
69. Sperandio M, Smith ML, Forlow SB, Olson TS, Xia L, McEver RP, and Ley K. P-selectin glycoprotein ligand-1 mediates L-selectin-dependent leukocyte rolling in venules. J Exp Med 197: 13551363, 2003.
70. Spertini O, Kansas GS, Munro JM, Griffin JD, and Tedder TF. Regulation of leukocyte migration by activation of the leukocyte adhesion molecule-1 (LAM-1) selectin. Nature 349: 691694, 1991.[CrossRef][ISI][Medline]
71. Steeber DA, Engel P, Miller AS, Sheetz MP, and Tedder TF. Ligation of L-selectin through conserved regions within the lectin domain activates signal transduction pathways and integrin function in human, mouse, and rat leukocytes. J Immunol 159: 952963, 1997.[Abstract]
72. Stein JV, Cheng G, Stockton BM, Fors BP, Butcher EC, and von Andrian UH. L-selectin-mediated leukocyte adhesion in vivo: microvillous distribution determines tethering efficiency, but not rolling velocity. J Exp Med 189: 3750, 1999.
73. Stewart MP, McDowall A, and Hogg N. LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain. J Cell Biol 140: 699707, 1998.
74. St Hill CA, Alexander SR, and Walcheck B. Indirect capture augments leukocyte accumulation on P-selectin in flowing whole blood. J Leukoc Biol 73: 464471, 2003.
75. Stulnig TM, Berger M, Sigmund T, Raederstorff D, Stockinger H, and Waldhausl W. Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains. J Cell Biol 143: 637644, 1998.
76. Taylor AD, Neelamegham S, Hellums JD, Smith CW, and Simon SI. Molecular dynamics of the transition from L-selectin- to 2-integrin-dependent neutrophil adhesion under defined hydrodynamic shear. Biophys J 71: 34883500, 1996.[Abstract]
77. Venturi GM, Tu L, Kadono T, Khan AI, Fujimoto Y, Oshel P, Bock CB, Miller AS, Albrecht RM, Kubes P, Steeber DA, and Tedder TF. Leukocyte migration is regulated by L-selectin endoproteolytic release. Immunity 19: 713724, 2003.[CrossRef][ISI][Medline]
78. Vestweber D and Blanks JE. Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79: 181213, 1999.
79. Von Andrian UH, Hasslen SR, Nelson RD, Erlandsen SL, and Butcher EC. A central role for microvillus receptor presentation in leukocyte adhesion under flow. Cell 82: 989999, 1995.[CrossRef][ISI][Medline]
80. Waddell TK, Fialkow L, Chan CK, Kishimoto TK, and Downey GP. Potentiation of the oxidative burst of human neutrophils. A signaling role for L-selectin. J Biol Chem 269: 1848518491, 1994.
81. Waddell TK, Fialkow L, Chan CK, Kishimoto TK, and Downey GP. Signaling functions of L-selectin: enhancement of tyrosine phosphorylation and activation of MAP kinase. J Biol Chem 270: 1540315411, 1995.
82. Walcheck B, Alexander SR, St Hill CA, and Matala E. ADAM-17-independent shedding of L-selectin. J Leukoc Biol 74: 389394, 2003.
83. Walcheck B, Kahn J, Fisher JM, Wang BB, Fisk RS, Payan DG, Feehan C, Betageri R, Darlak K, Spatola AF, and Kishimoto TK. Neutrophil rolling altered by inhibition of L-selectin shedding in vitro. Nature 380: 720723, 1996.[CrossRef][ISI][Medline]
84. Walcheck B, Leppanen A, Cummings RD, Knibbs RN, Stoolman LM, Alexander SR, Mattila PE, and McEver RP. The monoclonal antibody CHO-131 binds to a core 2 O-glycan terminated with sialyl-Lewis x, which is a functional glycan ligand for P-selectin. Blood 99: 40634069, 2002.
85. Walcheck B, Moore KL, McEver RP, and Kishimoto TK. Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1. A mechanism that amplifies initial leukocyte accumulation on P-selectin in vitro. J Clin Invest 98: 10811087, 1996.
86. Weis WI, Taylor ME, and Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev 163: 1934, 1998.[ISI][Medline]
87. Yarmola EG, Somasundaram T, Boring TA, Spector I, and Bubb MR. Actin-latrunculin A structure and function. Differential modulation of actin-binding protein function by latrunculin A. J Biol Chem 275: 2812028127, 2000.
88. Zollner O, Lenter MC, Blanks JE, Borges E, Steegmaier M, Zerwes HG, and Vestweber D. L-selectin from human, but not from mouse neutrophils binds directly to E-selectin. J Cell Biol 136: 707716, 1997.
|
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |