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Albumin transcytosis in mesothelium: further evidence of a transcellular pathway in polarized cells

Stephen M. Vogel and Asrar B. Malik

Department of Pharmacology, University of Illinois, College of Medicine, Chicago, Illinois 60612


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THE PREVAILING VIEW AMONG physiologists about fluid and protein exit from the pleural space is that most of it occurs via the lymphatic stomata of the parietal pleura under slightly subatmospheric intrapleural pressure (6, 8, 9). The pleura and other serosa, such as the pericardium and peritoneum, also possess a lining layer of mesothelial cells, whose function in the removal of fluid and protein from serous cavities has thus far been unclear. In this regard, early studies of isolated parietal or visceral pleura (mounted in an Ussing chamber) gave rather high permeability values to sucrose (Psuc) of 12-36 × 10-5 cm/s (4, 10). Such values, which are over an order of magnitude higher than those found in vascular endothelial cells, imply that liquid and small solutes are essentially freely permeable in serosal membranes.

Bodega et al. (Ref. 1a, see page L3 in this issue) now provide convincing evidence for the receptor-mediated transcytosis of albumin and fluid in the lumen-to-interstitium direction. The experimental findings, obtained using specimens of the rabbit parietal pericardium mounted in an Ussing chamber, can be briefly summarized: 1) apparent permeability to albumin (Palb) and permeability to dextran (Pdx) (used as a fluid-phase marker) were both temperature sensitive and were markedly reduced by nocodazole, an endocytosis inhibitor; 2) with physiological albumin concentration (1.0 g/100 ml), active albumin flux was ~5 × 10-4 M/(h cm2), but was essentially zero at the threshold albumin concentration of 0.005 g/100 ml; 3) there was a transcytic flow of liquid of 3.5 µl/(h cm2), calculated from the experimentally determined flux of the fluid-phase marker; and 4) albumin flux in the interstitium-to-luminal direction was passive and less than the albumin flux in the opposing direction.

These findings of Bodega et al. (1a) are intriguing because they suggest that albumin activates its own transcytosis through mesothelial cells, perhaps via fluid-filled vesicular carriers that mediate a net transport of protein and liquid from lumen to interstitium. Indeed, free cytoplasmic vesicles have been noted to occur in mesothelial cells in earlier morphological studies (3, 5). The presumptive fate of the albumin and liquid transported into the interstitium is eventually to be drained by the lymphatics of the interstitial space (1). A natural question that arises is why such a mechanism was overlooked in previous studies. Zocchi et al. (15) obtained much lower values for Psuc (× 10-5 cm/s), ranging from 2.2 to 2.6 when care was taken to preserve the mesothelial cell layer; this was greatly facilitated by taking specimens from the sternal aspect of the parietal pericardium, a fairly free region of pericardium that is less susceptible to the damaging effects of being "stripped" from surrounding tissues. Based on these data, Zocchi et al. (15) concluded that most of the resistance to the diffusion of small molecules in the pericardium is provided by the mesothelial cell layer.

Because of the clear dependence of albumin transcytosis on the luminal albumin concentration, it is apparent that this form of vesicular transport is not constitutive in mesothelium, but rather is activated by albumin. There are, in fact, analogous phenomena in vascular endothelial cells where an albumin binding protein (gp60 or albondin) has been postulated to act as a receptor or docking molecule for albumin (11, 13, 14). Gp60 is probably localized in endothelial caveolae in some association with caveolin-1 (2, 12). The binding of albumin to gp60 (or activation of gp60 using a cross-linking antibody) was shown to activate the transcytosis of albumin in a manner involving Gi-linked Src kinase signaling (7). The nature and function of albumin-binding proteins on the mesothelial cell surface represent an exciting topic for future research on albumin transcytosis and how plasma-lemma-derived vesicles are formed at the cell surface and directed to the opposite membrane without avoiding lysosomes and other intracellular compartments. The obvious question arises whether the mechanisms of albumin transcytosis in the mesothelium and endothelium utilize the same albumin-docking protein(s) and signaling machinery. The answer to this question will help to further define the physiological relevance of this potentially important transport process in polarized cells.


    FOOTNOTES

Address for reprint requests and other correspondence: A. B. Malik, Dept. of Pharmacology, Univ. of Illinois, College of Medicine, 835 S. Wolcott Ave., Chicago, IL 60612.


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1a.   Bodega, F, Zocchi L, and Agostoni E. Albumin transcytosis in mesothelium. Am J Physiol Lung Cell Mol Physiol 282: L3-L11, 2002[Abstract/Free Full Text].

2.   Ghitescu, L, Fixman A, Simionescu M, and Simionescu N. Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis. J Cell Biol 102: 1304-1311, 1986[Abstract].

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7.   Minshall, RD, Tiruppathi C, Vogel SM, Niles WD, Gilchrist A, Hamm HE, and Malik AB. Endothelial cell-surface gp60 activates vesicle formation and trafficking via G(i)-coupled Src kinase signaling pathway. J Cell Biol 150: 1057-1070, 2000[Abstract/Free Full Text].

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11.   Schnitzer, JE, and Oh P. Albondin-mediated capillary permeability to albumin. Differential role of receptors in endothelial transcytosis and endocytosis of native and modified albumins. J Biol Chem 269: 6072-6082, 1994[Abstract/Free Full Text].

12.   Schnitzer, JE, Oh P, Pinney E, and Allard J. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J Cell Biol 127: 1217-1232, 1994[Abstract].

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15.   Zocchi, L, Raffaini A, Agostoni E, and Cremaschi D. Diffusional permeability of rabbit mesothelium. J Appl Physiol 85: 471-477, 1998[Abstract/Free Full Text].


Am J Physiol Lung Cell Mol Physiol 282(1):L1-L2
1040-0605/02 $5.00 Copyright © 2002 the American Physiological Society




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