AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 4 578-G583, Copyright © 1990 by American Physiological Society
Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules
P. R. Kvietys, M. A. Perry, T. S. Gaginella and D. N. Granger
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
In vivo studies have implicated neutrophils in the gastric mucosal injury
produced by intraluminal administration of ethanol. However, in vitro
studies indicate that ethanol inhibits various neutrophil functions such as
adherence, chemotaxis, and degranulation. The aim of the present study was
to assess whether ethanol, at clinically relevant concentrations, is
proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to
the surface of the cat mesentery, and neutrophil adherence to venules (30
microns diam) and extravasation into the interstitium were quantitated
using intravital microscopy. Hemodynamic parameters were also measured
(venular diameter, red blood cell velocity, and leukocyte rolling velocity)
or calculated (venular blood flow and wall shear stress). In this model
ethanol produced a dose-dependent increase in neutrophil adherence and
extravasation. The increase in leukocyte-endothelial cell interactions
could not be attributed to alterations in hemodynamic factors. Pretreatment
of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil
CD11/CD18 adherence complex completely prevented the ethanol-induced
neutrophil adherence and extravasation. Pretreatment with a leukotriene B4
(LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor
(PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced
neutrophil-endothelial interactions. We conclude that ethanol is
proinflammatory at concentrations which may be achieved in the mucosal
interstitium during acute alcohol intoxication. The ethanol-induced
leukocyte adherence and extravasation is dependent on the expression of
adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not
appear to play an important role in the leukocyte-endothelial cell
interactions initiated by ethanol.
