Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules.
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.
Kvietys
P R
PR
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Perry
M A
MA
Gaginella
T S
TS
Granger
D N
DN
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000502:physiology; D008642:Mesenteric Veins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D014699:Venules / Q000502:physiology*; D014743:Videotape Recording
D001578:Benzopyrans; D010972:Platelet Activating Factor; C059950:SC 41930; D000431:Ethanol