EDITORIAL FOCUS
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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ARTICLE |
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.
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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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