Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats.
The objective of this study was to define the influence of hypercholesterolemia on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules. The microvascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more pronounced in hypercholesterolemic rats (compared with control rats). Monoclonal antibodies against the adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-selectin-specific antibody. Platelet aggregation was reduced by antibodies directed against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion-induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte-endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to influence the extravasation of both leukocytes and albumin in postischemic venules of hypercholesterolemic rats.
Kurose
I
I
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Argenbright
L W
LW
Anderson
D C
DC
Tolley
J
J
Miyasaka
M
M
Harris
N
N
Granger
D N
DN
D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion; D002465:Cell Movement; D006937:Hypercholesterolemia / Q000097:blood* / Q000503:physiopathology*; D007511:Ischemia / Q000097:blood / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000097:blood* / Q000503:physiopathology*; D010973:Platelet Adhesiveness; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012709:Serum Albumin / Q000493:pharmacokinetics; D013152:Splanchnic Circulation
D012709:Serum Albumin