Departments of Biochemistry and Molecular Biology 1 I and 3 III, and 2 Department of Surgery, San Carlos Hospital, Complutense University of Madrid, 28040 Madrid, Spain
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this study we
investigated the effect of acute-phase levels of C-reactive protein
(CRP) on cytokine production by pulmonary macrophages in the presence
or absence of pulmonary surfactant. Both human alveolar and
interstitial macrophages as well as human surfactant were obtained from
multiple organ donor lungs. Precultured macrophages were stimulated
with LPS alone or together with IFN- in the presence or absence of
CRP, surfactant, and combinations. Releases of TNF-
and of IL-1
to the medium were determined. We found that CRP could modulate lung
inflammation in humans by decreasing the production of proinflammatory
cytokines by both alveolar and interstitial macrophages stimulated with
LPS alone or together with IFN-
. The potential interaction between
CRP and surfactant phospholipids did not overcome the effect of either CRP or surfactant on TNF-
and IL-1
release by lung macrophages. On the contrary, CRP and pulmonary surfactant together had a greater inhibitory effect than either alone on the release of proinflammatory cytokines by lung macrophages.
human lung surfactant; interstitial macrophages; alveolar macrophages; lipopolysaccharide
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
C-REACTIVE
PROTEIN (CRP) is a member of the pentraxin family of plasma
proteins. These proteins are highly conserved in evolution and precede
the development of the adaptive immune response (12). They
are made up of five identical globular subunits arranged in a cyclic
pentamer shape appearing as a doughnut in electron imaging
(31). All pentraxins bind two Ca2+ per
subunit, which are necessary for expression of phosphocholine binding
activity (34). CRP binds to the pneumococcal cell wall C-polysaccharide, other phosphocholine-containing polysaccharides present in the cell surface of various gram-negative bacteria, and
Mycoplasma, as well as phosphatidylcholine in lipid bilayers (34). CRP also binds to C1q (31) and
phagocytic cells in mice and in humans (39, 32) through FC
receptors. FcRIa, the high-affinity IgG receptor, binds CRP with low
affinity, whereas Fc
RIIa, the low-affinity IgG receptor, binds CRP
with high affinity (30). It is proposed that the binding
site of CRP to C1q or cells is located on the face of each subunit
opposite the phosphocholine-binding site (31).
CRP is considered the prototypical acute-phase reactant in humans. The synthesis and secretion of CRP notably increases in serum following tissue injury, infection, or inflammation (12). Normal human serum concentrations of CRP are <1 µg/ml; however, after inflammation or sepsis, serum levels can increase as much as 1,000-fold (12, 17). The magnitude of this increase correlates with the extent of tissue injury or the severity of the inflammatory state. CRP is produced predominantly by hepatocytes in response to proinflammatory cytokines (12). Alveolar macrophages can also produce and secrete CRP to the alveolar space (11). The CRP mRNA levels in isolated macrophages are upregulated by in vitro lipopolysaccharide (LPS) stimulation (11). Patients with sepsis-induced acute respiratory distress syndrome (ARDS) have elevated levels of CRP in both plasma and the bronchoalveolar lavage (BAL) (17, 20). In addition, elevated levels of CRP are found in pulmonary surfactant from transplanted lungs (10).
The increased concentration of CRP in both serum and alveolar fluid
after inflammation or sepsis suggests that it fulfills an important
biological role. Many of the known properties of CRP are manifested by
its interactions with immunologic effector systems. CRP activates the
complement system via the classic pathway, promotes phagocytosis and
activation of platelets, and enhances LPS-induced production of
interleukin (IL)-1 by human blood monocytes (12). These
data are consistent with proinflammatory action of CRP in serum.
However, the precise function of CRP in the alveolar fluid remains
unclear. There is controversy over whether CRP enhances or suppresses
the host inflammatory response to LPS in the alveolar space (13,
25). In these studies, the interaction of CRP with alveolar
macrophages was studied in the absence of pulmonary surfactant, a
membranous material that lines the alveolar epithelium and the alveolar macrophages.
We recently found that CRP present in the cell-free BAL of transplanted
lungs is recovered in the floating pulmonary surfactant fraction
(10), indicating that CRP binds to surfactant membranes. Because CRP binds avidly to these membranes, it is reasonable to think
that surfactant membranes could affect the mode of CRP presentation to
its receptors on macrophages. The first objective of the present study
was to explore whether CRP stimulates or decreases the inflammatory
response of human lung macrophages activated with LPS or the
combination LPS and interferon (IFN)-. The second objective was to
investigate whether pulmonary surfactant affects the CRP-mediated
cytokine production by pulmonary macrophages. These studies were done
in both human interstitial and alveolar macrophages. Although alveolar
macrophages are continuously in contact with pulmonary surfactant in
vivo, interstitial macrophages contact surfactant particularly during
lung inflammation because the alveolar epithelium is disrupted.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Human lung tissue procurement. As a source of lung tissue we used male multiple organ donors. The review board and the ethics committee of the San Carlos Hospital approved this study. Ages ranged from 19 to 50 yr, and cranial trauma or spontaneous intracranial hemorrhage was the cause of death in all of them. Donors with recent history of tobacco smoking, >72 h of mechanical ventilation, or any radiological pulmonary infiltrate were excluded from this study. Immediately after obtaining the left lung, we performed a BAL at 4°C, and the lung was then placed in cold saline solution. The cold ischemia period was <3 h in all cases.
Isolation and analysis of human surfactant. Pulmonary surfactant from human lungs was obtained as previously described (9, 10). Briefly, cell-free BAL was centrifuged at 100,000 g for 2 h at 4°C to obtain the large surfactant aggregates in the resulting pellet. The separation of pulmonary surfactant from blood components was performed by NaBr density-gradient centrifugation at 116,000 g for 2 h at 4°C. Surfactant has a density of ~1.085 at 4°C, which is lower than that of most of the contaminating components of serum.
Total phospholipid was determined from aliquots of both surfactant and lipid extracts of surfactant by phosphorus analysis as described by Rouser et al. (26). Surfactant concentration was expressed in terms of phospholipid concentration. Total surfactant cholesterol was determined enzymatically with the Sigma diagnostic cholesterol kit. Total proteins in human surfactant was measured with the method of Lowry and associates (21). Human surfactant apolipoproteins (SP)-A, SP-B, and SP-C were detected in large surfactant aggregates by Western blotting analysis. Electrophoretic analysis of surfactant was performed under reducing conditions (5%Cell isolation and culture.
Bronchoalveolar cells were separated from lavage fluid by
centrifugation. The sedimented cells were washed twice with HBSS. Cell
suspension was centrifuged (250 g, 10 min), and the cell pellet was resuspended in RPMI 1640 medium (10% heat-inactivated FCS,
100 IU/ml penicillin G, and 50 µg/ml gentamicin). Alveolar macrophages were purified by adherence for 90 min at 37°C under a
95% air-5% CO2 atmosphere in RPMI 1640 medium in
75-cm2 culture flasks. Macrophages from lung interstitium
were isolated as described elsewhere (4, 7). Briefly,
tissue fragments underwent an enzymatic digestion with elastase (27 U/ml) in a 37°C shaking bath for 60 min. Digestion was stopped by
addition of 4°C FCS. The tissue was filtered through nylon mesh (200 and 20 µm), and the cell suspension was washed twice with HBSS and centrifuged (250 g, 10 min). The cell pellets were
resuspended in RPMI 1640 medium, and poured into 75-cm2
culture flasks. Interstitial macrophages were also purified by adherence. After 90 min of incubation (37°C, under
O2-CO2 atmosphere), the supernatants were
removed and the cells were washed four times with phosphate-buffered
saline to remove contaminating nonadherent cells. Adherent cells were
found to be 99.5 ± 0.3% viable (trypan blue exclusion test) and
composed of 92.5 ± 3.1% macrophages, as judged by
Wright-Giemsa-stained cytocentrifuge preparations. Flow cytometry
analysis of macrophages immunostained with anti-HLA-DR and antibodies
to CD14 confirmed the purity of macrophage preparations. The cells were
gently scraped, plated onto collagen-coated 96-well plastic dishes
(5 × 105 cells per well), and precultured for 24 h. Under these conditions, ~95% of the cells were attached; cell
viability was >97%, and macrophage purity was always >98%. Cells
were cultured for another 24 h in the presence or absence of
smooth LPS (Escherichia coli 0111:B4, 10 µg/ml), LPS + IFN- (100 U/ml), human CRP (Calbiochem), human surfactant, and
combinations. Human CRP preparations were tested for bacterial
endotoxin using a Limulus amebocyte lysate assay
(Bio-Whittaker, Walkersville, MD). Human CRP contained 0.53 ± 0.11 pg endotoxin/µg protein. The amount of contaminating LPS from
the CRP source was not significant compared with the LPS concentration
used in this study.
Cytokine assays.
Cell-free culture supernatants were collected and assayed for TNF-
and IL-1
with enzyme-linked immunoassay kits (Biosource International). An aliquot of the cell suspension was used for protein
quantification, performed by the Coomassie brilliant blue dye method.
Statistical analyses.
The number of separate macrophage preparations (n 6)
employed (each from a different donor lung) is represented by
n. The assays from each macrophage preparation were
performed at least twice, the replicate values were averaged, and their
mean was treated as a single point. The results are presented as the
means ± SE, obtained by combining the results from each cell
preparation. Mean comparison was done by Friedman's analysis of
variance of ranks, followed by a two-tailed Wilcoxon's rank sum test
for paired data to identify the source of the found differences; a
confidence level of
95% (P < 0.05) was considered significant.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Effect of CRP on TNF- and IL-1
production by human lung
macrophages.
CRP levels highly increase in both BAL fluid (20) and
serum (17) from patients with ARDS. Furthermore, patients
who survived the acute lung injury tended to have more CRP levels in
their blood and BAL fluid than those patients who died
(18). Therefore, we investigated the dose-response effect
of human CRP on human lung macrophages at acute-phase levels of CRP
(125 and 250 µg/ml). Figure 1 shows
that unstimulated alveolar and interstitial macrophages isolated from
nine different donors produced low concentrations of TNF-
and
IL-1
after 24 h of culture in the absence or presence of
acute-phase levels of CRP (125 and 250 µg/ml). The production of
TNF-
and IL-1
by either interstitial or alveolar macrophages greatly increased after 24 h of culture in the presence of LPS; that increase was even greater when macrophages were incubated with
IFN-
together with LPS. The addition of 125 µg/ml CRP to alveolar
macrophages significantly inhibited LPS-induced production of TNF-
(by 67%) and IL-1
(by 60%). CRP caused TNF-
release inhibition
of 85% and IL-1
release inhibition of 70% when these cells were
stimulated with LPS + IFN-
. The effect of 125 µg/ml CRP on
TNF-
and IL-1
production by stimulated interstitial macrophages was less pronounced; CRP (125 µg/ml) caused an inhibition of TNF-
and IL-1
production of ~50%. However, at higher levels of CRP (250 µg/ml), TNF-
and IL-1
production by both interstitial and alveolar macrophages, stimulated with IFN-
and/or LPS, was inhibited by >80%. These data indicate that CRP could modulate lung
inflammation in humans by decreasing the LPS-induced production of
proinflammatory cytokines by both interstitial and alveolar
macrophages.
|
Human surfactant analysis.
Pulmonary surfactant is a complex material that contains several
specific apolipoproteins (SP-A, SP-B, and SP-C) and a variety of
lipids, in particular a high proportion (~80%) of
phosphatidylcholine. Different components of surfactant have very
different effects on the modulation of immune cell function
(38). Because of the complexity of these
membranes, we analyzed some lipid characteristics of human surfactants
used in this study (Table 1). Human
surfactant appears to contain a higher cholesterol-to-phospholipid
molar ratio compared with surfactant membranes from other mammalian species (36). The presence of surfactant apolipoproteins
in samples of human surfactant was determined by immunoblot analysis of
SP-A, SP-B, and SP-C (Fig. 2). SP-A
immunoreactive bands of ~35 and ~70 kDa were detected in all
surfactant samples analyzed. The nonreducible dimer (~70 kDa),
described for SP-A isolated from alveolar proteinosis patients, is also
characteristic of human SP-A from healthy persons. Monomeric SP-C, but
not dimeric/depalmitoylated SP-C [found in surfactants from alveolar
proteinosis patients (16)], was detected. SP-B consisted
of dimers of ~18 kDa and higher oligomeric forms under nonreducing
conditions. Only monomeric SP-B (~9 kDa) was recognized under
reducing conditions.
|
|
Effect of pulmonary surfactant on CRP modulation of proinflammatory
cytokines production by interstitial and alveolar macrophages.
Because CRP binds avidly to surfactant membranes, we next investigated
the effect of these membranes on CRP-modulation of both TNF- and
IL-1
production by lung macrophages. Figure
3 shows that unstimulated interstitial
and alveolar macrophages isolated from six different donors produced
low concentrations of TNF-
after 24 h of culture in the absence
or presence of acute-phase levels of CRP (125 µg/ml), human pulmonary
surfactant (0.5 mM), or the combination of pulmonary surfactant and CRP
(3:1 weight ratio). Figure 3 also indicates that the addition of
surfactant membranes to interstitial or alveolar macrophages
significantly inhibited the production of TNF-
by these cells
stimulated by LPS alone or LPS together with IFN-
. The incubation of
these cells with pulmonary surfactant together with CRP led to a
greater decrease in the production of TNF-
by both interstitial and
alveolar macrophages stimulated with LPS alone or together with
IFN-
.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The present study indicates that 1) CRP could modulate
lung inflammation in humans by decreasing the production of
proinflammatory cytokines by both interstitial and alveolar macrophages
stimulated with LPS alone or together with IFN- and 2)
the potential interaction between CRP and surfactant phospholipids did
not overcome the effect of either CRP or pulmonary surfactant on
TNF-
and IL-1
release by lung macrophages. On the contrary, both
together had a greater inhibitory effect than either alone on the
release of proinflammatory cytokines by lung macrophages.
Our observation that CRP decreased TNF- secretion from
LPS-stimulated alveolar macrophages is in agreement with the data from
Pue and colleagues (25), who indicated that acute-phase levels of CRP downregulated human alveolar macrophage production of
IL-1
in response to endotoxins. However, our results appears to
contradict the data from Galve-de Rochemonteix et al.
(13), who showed an enhancement of the human alveolar
macrophage production of cytokines after stimulation by CRP. Although
our study focused on the effects of CRP on LPS-activated interstitial
and alveolar macrophages, we did test the ability of CRP to induce
production of TNF-
and IL-1
by unstimulated cells. We could not
detect any significant increase in the baseline liberation of these
cytokines. We currently have no unequivocal explanation for these
contrasting results, although there were some differences in
experimental design. A major difference in the two studies is the
dissimilar origin of human alveolar macrophages. In the study by
Galve-de Rochemonteix et al., alveolar macrophages were obtained
from patients with pulmonary cell carcinoma. Alveolar macrophages from
patients with lung cancer have shown in vitro greater TNF-
and IL-1
secretion than healthy controls (3, 28). In the present
study, these cells were obtained from previously healthy organ donors.
In addition, we performed parallel experiments with interstitial
macrophages, which reside within the interstitial space and are thought
to be precursors of alveolar macrophages. These cells are not solely an
intermediate maturation stage of alveolar macrophages but contribute actively to the process of inflammation in the lung, with potential beneficial or destructive effects on the surrounding tissue
(8). To our knowledge, all previous studies involving
interactions of CRP with lung macrophages were carried out with the
alveolar variety. The present study demonstrates that CRP has an
inhibitory effect on the release of proinflammatory cytokines by both
alveolar and interstitial macrophages.
Neutrophil accumulation and vascular permeability are common events in ARDS, and CRP appears to offer a protective effect in this disease (18). In animal models of inflammation-mediated lung injury, CRP acts as an anti-inflammatory agent mediating inhibition of neutrophil alveolitis and vascular permeability (17). However, the mechanism by which CRP elicits this inhibitory effect is undefined. The downregulation of proinflammatory cytokine production by macrophages could be involved in the inhibition of neutrophil alveolitis.
The alveolar fluid from normal lungs contains low levels of CRP and a high concentration of pulmonary surfactant, which is involved in reducing the surface tension of the fluid lining the alveoli and in host defense (37). The large excess of SP-A and surfactant membranes (containing SP-B and SP-C) in normal air spaces probably minimizes the biological effects of the low concentration of endotoxins that enter the alveolus. Given the lipophilic nature of LPS, it might incorporate in surfactant membranes, making LPS unavailable for signaling. The hydrophobic surfactant protein SP-C interacts with LPS (5, 6), indicating that this surfactant component could participate in the recognition and neutralization of inhaled LPS. On the other hand, SP-A, the most abundant surfactant apolipoprotein, might mediate inhibition of LPS-induced activation by either direct interaction of SP-A with cellular binding sites of immune cells (in the case of smooth LPS) (27) or direct interaction with LPS (in the case of rough LPS), which blocks the binding of rough LPS to LPS-binding protein (LBP); this prevents the initiation of the LBP/CD14 pathway for inflammatory responses to rough LPS (29).
In patients with acute lung injury in which proinflammatory cytokines
and neutrophils accumulate in the air spaces, the concentration of SP-A
and surfactant lipids decreases, whereas the concentration of CRP and
LBP rises 100-fold or more (17, 22). Although LBP would
likely amplify the biological effect of LPS in the lungs, CRP would
limit excessive proinflammatory cytokine release by LPS-stimulated
alveolar macrophages. We found that the inhibitory effect of CRP on the
release of proinflammatory cytokines by stimulated human lung
macrophages was not reduced but strengthened by interaction with
surfactant membranes. The interaction of CRP with these membranes could
favor the mode of presentation and binding of CRP to its receptors on
macrophages. CRP molecules are known from electron microscopy to form
ordered two-dimensional arrays at surfaces, and this effect is likely
to occur on the lipid bilayer. Furthermore, CRP binds to cells and/or
effector molecules via the face of its subunits opposite to the face
where the specific site for phosphocholine head groups of phospholipids
on membranes is located (31, 34). On the other hand, the
fact that CRP and pulmonary surfactant together had a greater
inhibitory effect than either alone on the release of proinflammatory
cytokines could also be explained by an additive effect. In support of
this possibility, we recently found that human SP-A from normal
subjects inhibits the smooth LPS-induced TNF- response of both human
interstitial and alveolar macrophages when assayed alone
(2) or in the presence of
dipalmitoyl-L-
-phosphatidylcholine vesicles (C. Casals, J. Arias-Díaz, and E. Vara, unpublished results). However, the smooth LPS-elicited release of IL-1
in human alveolar macrophages is not suppressed by human SP-A
(2) but by a synthetic surfactant (Exosurf)
(33) or bovine-derived surfactant lipid extracts
(Survanta) containing the hydrophobic surfactant proteins SP-B and SP-C
(1).
ARDS represents an enormous clinical problem that is therapeutically unresolved. Because alterations in the surfactant system significantly contribute to the pathophysiology of the lung injury of patients with ARDS, surfactant replacement therapy has been used in many animal models of lung injury with some encouraging results (19, 37). Alternatively, the potential therapeutic use of CRP in the treatment of inflammation-mediated lung diseases in humans has been proposed (17). However, a high CRP-to-surfactant phospholipid weight ratio might be harmful for the lung function because the binding of CRP to surfactant membranes inhibits the tension-reducing properties of surfactant (10, 23). Future studies will investigate the mechanism by which CRP inhibits LPS-induced activation of lung macrophages. In addition, experiments are in progress to determine whether specific interactions of CRP with surfactant components influence CRP-mediated inhibitory effects on cytokine production.
![]() |
ACKNOWLEDGEMENTS |
---|
We are grateful to Professor Klaus P. Schäfer and Dr. Wolfram Steinhilber (Altana Pharma AG, Byk-Gulden-Str. 2, 78467 Konstanz, Germany) for providing polyclonal antibody against recombinant human SP-C. We also thank Rosario del Barrio and Joaquin Alvarez for collaboration in obtaining the lungs.
![]() |
FOOTNOTES |
---|
F. Valiño was recipient of a Universidad Complutense de Madrid grant. A. Saenz is recipient of a grant from Lab. Esteve, S. A. (Barcelona). This work was supported by Comisíon Interministerial de Ciencia y Tecnologia Grant PB98-0769, Comunidad of Madrid Grant CAM-08.3/0008/2000, and European Community Grant QLK2-CT-2000-00325.
Present address for F. Valiño: Dept. of Pharmacology, University of California, Irvine, CA 92697-4625.
Address for reprint requests and other correspondence: C. Casals, Dept. of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense Univ. of Madrid, 28040 Madrid, Spain (E-mail: ccasalsc{at}bio.ucm.es).
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.
First published November 15, 2002;10.1152/ajplung.00325.2002
Received 26 September 2002; accepted in final form 11 November 2002.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Allen, JN,
Moore SA,
Pope-Harman AL,
Marsh CB,
and
Wewers MD.
Immunosuppressive properties of surfactant and plasma on alveolar macrophages.
J Lab Clin Med
125:
356-369,
1995[ISI][Medline].
2.
Arias-Diaz, J,
Garcia-Verdugo I,
Casals C,
Sanchez-Rico N,
Vara E,
and
Balibrea JL.
Effect of surfactant protein A (SP-A) on the production of cytokines by human pulmonary macrophages.
Shock
14:
300-306,
2000[ISI][Medline].
3.
Arias-Diaz, J,
Vara E,
Garcia C,
and
Balibrea JL.
Tumor necrosis factor-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes is partially mediated by prostaglandins.
J Clin Invest
94:
244-250,
1994[ISI][Medline].
4.
Arias-Diaz, J,
Vara E,
Garcia C,
Villa N,
and
Balibrea JL.
Evidence for a cyclic guanosine monophosphate-dependent, carbon monoxide-mediated, signaling system in the regulation of TNF-alpha production by human pulmonary macrophages.
Arch Surg
130:
1287-1293,
1995[Abstract].
5.
Augusto, L,
Le Blay K,
Auger G,
Blanot D,
and
Chaby R.
Interaction of bacterial lipopolysaccharide with mouse surfactant protein C inserted into lipid vesicles.
Am J Physiol Lung Cell Mol Physiol
281:
L776-L785,
2001
6.
Augusto, LA,
Li J,
Synguelakis M,
Johansson J,
and
Chaby R.
Structural basis for interactions between lung surfactant protein C and bacterial lipopolysaccharide.
J Biol Chem
277:
23484-23492,
2002
7.
Balibrea, JL,
Arias-Diaz J,
Garcia C,
and
Vara E.
Effect of pentoxifylline and somatostatin on tumour necrosis factor production by human pulmonary macrophages.
Circ Shock
43:
51-56,
1994[ISI][Medline].
8.
Bezdicek, P,
and
Crystal RG.
Pulmonary macrophages.
In: The Lung: Scientific foundations, edited by Crystal RG,
West JB,
Barnes PJ,
and Weibel ER.. New York: Lippincott-Raven, 1997, p. 859-875.
9.
Casals, C,
Herrera L,
Miguel E,
Garcia-Barreno P,
and
Municio AM.
Comparison between intra- and extracellular surfactant in respiratory distress induced by oleic acid.
Biochim Biophys Acta
1003:
201-203,
1989[ISI][Medline].
10.
Casals, C,
Varela A,
Ruano ML,
Valino F,
Perez-Gil J,
Torre N,
Jorge E,
Tendillo F,
and
Castillo-Olivares JL.
Increase of C-reactive protein and decrease of surfactant protein A in surfactant after lung transplantation.
Am J Respir Crit Care Med
157:
43-49,
1998
11.
Dong, Q,
and
Wright JR.
Expression of C-reactive protein by alveolar macrophages.
J Immunol
156:
4815-4820,
1996
12.
Du Clos, TW.
Function of C-reactive protein.
Ann Med
32:
274-278,
2000[ISI][Medline].
13.
Galve-de Rochemonteix, B,
Wiktorowicz K,
Kushner I,
and
Dayer JM.
C-reactive protein increases production of IL-1 alpha, IL-1 beta, and TNF-alpha, and expression of mRNA by human alveolar macrophages.
J Leukoc Biol
53:
439-445,
1993[Abstract].
14.
Geertsma, MF,
Teeuw WL,
Nibbering PH,
and
van Furth R.
Pulmonary surfactant inhibits activation of human monocytes by recombinant interferon-gamma.
Immunology
82:
450-456,
1994[ISI][Medline].
15.
Gregory, TJ,
Longmore WJ,
Moxley MA,
Whitsett JA,
Reed CR,
Fowler AA, III,
Hudson LD,
Maunder RJ,
Crim C,
and
Hyers TM.
Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.
J Clin Invest
88:
1976-1981,
1991[ISI][Medline].
16.
Gustafsson, M,
Thyberg J,
Naslund J,
Eliasson E,
and
Johansson J.
Amyloid fibril formation by pulmonary surfactant protein C.
FEBS Lett
464:
138-142,
1999[ISI][Medline].
17.
Heuertz, RM,
and
Webster RO.
Role of C-reactive protein in acute lung injury.
Mol Med Today
3:
539-545,
1997[ISI][Medline].
18.
Kew, RR,
Hyers TM,
and
Webster RO.
Human C-reactive protein inhibits neutrophil chemotaxis in vitro: possible implications for the adult respiratory distress syndrome.
J Lab Clin Med
115:
339-345,
1990[ISI][Medline].
19.
Lewis, JF,
and
Jobe AH.
Surfactant and the adult respiratory distress syndrome.
Am Rev Respir Dis
147:
218-233,
1993[ISI][Medline].
20.
Li, JJ,
Sanders RL,
McAdam KP,
Hales CA,
Thompson BT,
Gelfand JA,
and
Burke JF.
Impact of C-reactive protein (CRP) on surfactant function.
J Trauma
29:
1690-1697,
1989[ISI][Medline].
21.
Lowry, OH,
Rosebrough NJ,
Farr AL,
and
Randall RJ.
Protein measurement with the Folin phenol reagent.
J Biol Chem
193:
265-275,
1951
22.
Martin, TR.
Recognition of bacterial endotoxin in the lungs.
Am J Respir Cell Mol Biol
23:
128-132,
2000
23.
McEachren, TM,
and
Keough KM.
Phosphocholine reverses inhibition of pulmonary surfactant adsorption caused by C-reactive protein.
Am J Physiol Lung Cell Mol Physiol
269:
L492-L497,
1995
24.
Pérez-Gil, J,
Cruz A,
and
Casals C.
Solubility of hydrophobic surfactant proteins in organic solvent/water mixtures. Structural studies on SP-B and SP-C in aqueous organic solvents and lipids.
Biochim Biophys Acta
1168:
261-270,
1993[ISI][Medline].
25.
Pue, CA,
Mortensen RF,
Marsh CB,
Pope HA,
and
Wewers MD.
Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar macrophages.
J Immunol
156:
1594-1600,
1996[Abstract].
26.
Rouser, G,
Freischer S,
and
Yamamoto A.
Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots.
Lipids
5:
494-496,
1970[ISI][Medline].
27.
Sano, H,
Sohma H,
Muta T,
Nomura S,
Voelker DR,
and
Kuroki Y.
Pulmonary surfactant protein A modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14.
J Immunol
163:
387-395,
1999
28.
Siziopikou, KP,
Harris JE,
Casey L,
Nawas Y,
and
Braun DP.
Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer.
Cancer
68:
1035-1044,
1991[ISI][Medline].
29.
Stamme, C,
Muller M,
Hamann L,
Gutsmann T,
and
Seydel U.
Surfactant protein A inhibits lipopolysaccharide-induced immune cell activation by preventing the interaction of lipopolysaccharide with lipopolysaccharide-binding protein.
Am J Respir Cell Mol Biol
27:
353-360,
2002
30.
Stein, MP,
Edberg JC,
Kimberly RP,
Mangan EK,
Bharadwaj D,
Mold C,
and
Du Clos TW.
C-reactive protein binding to FcRIIa on human monocytes and neutrophils is allele-specific.
J Clin Invest
105:
369-376,
2000
31.
Szalai, AJ,
Agrawal A,
Greenhough TJ,
and
Volanakis JE.
C-reactive protein: structural biology and host defense function.
Clin Chem Lab Med
37:
265-270,
1999[ISI][Medline].
32.
Tebo, JM,
and
Mortensen RF.
Characterization and isolation of a C-reactive protein receptor from the human monocytic cell line U-937.
J Immunol
144:
231-238,
1990
33.
Thomassen, MJ,
Meeker DP,
Antal JM,
Connors MJ,
and
Wiedemann HP.
Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages.
Am J Respir Cell Mol Biol
7:
257-260,
1992[ISI][Medline].
34.
Thompson, D,
Pepys MB,
and
Wood SP.
The physiological structure of human C-reactive protein and its complex with phosphocholine.
Structure
7:
169-177,
1999[ISI][Medline].
35.
Towbin, H,
Staehelin T,
and
Gordon J.
Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
Proc Natl Acad Sci USA
76:
4350-4354,
1979[Abstract].
36.
Veldhuizen, R,
Nag K,
Orgeig S,
and
Possmayer F.
The role of lipids in pulmonary surfactant.
Biochim Biophys Acta
1408:
90-108,
1998[ISI][Medline].
37.
Wiswell, TE,
Smith RM,
Katz LB,
Mastroianni L,
Wong DY,
Willms D,
Heard S,
Wilson M,
Hite RD,
Anzueto A,
Revak SD,
and
Cochrane CG.
Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome.
Am J Respir Crit Care Med
160:
1188-1195,
1999
38.
Wright, JR.
Immunomodulatory functions of surfactant.
Physiol Rev
77:
931-962,
1997
39.
Zahedi, K,
Tebo JM,
Siripont J,
Klimo GF,
and
Mortensen RF.
Binding of human C-reactive protein to mouse macrophages is mediated by distinct receptors.
J Immunol
142:
2384-2392,
1989
|
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |