Document Detail

Molecular determinants of reperfusion-induced leukocyte adhesion and vascular protein leakage.
MedLine Citation:
PMID:  7507416     Owner:  NLM     Status:  MEDLINE    
The adherence and emigration of leukocytes have been implicated as a rate-limiting step in the microvascular dysfunction associated with reperfusion of ischemic tissues. The objective of the present study was to define the relation between leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules exposed to ischemia and reperfusion (I/R). Leukocyte adherence and emigration as well as albumin extravasation were monitored in single post-capillary venules using intravital fluorescence microscopy. Ischemia (0, 10, 15, or 20 minutes) was induced by complete occlusion of the superior mesenteric artery, and all parameters were monitored for 30 minutes after reperfusion. The magnitude of the leukocyte adherence and emigration and albumin leakage elicited by I/R was positively correlated with the duration of ischemia. The albumin leakage response was also highly correlated with the number of adherent and emigrated leukocytes. Monoclonal antibodies against the adhesion glycoproteins CD18, CD11b, intercellular adhesion molecule-1 (ICAM-1) (at 10 and 30 minutes), and L-selectin (at 10 minutes), but not P- or E-selectin, reduced I/R-induced leukocyte adherence and emigration as well as albumin leakage. Platelet-leukocyte aggregates were formed in postischemic venules; the number of aggregates was reduced by antibodies against P-selectin, CD11b, CD18, and ICAM-1, but not E- or L-selectin. These results indicate that reperfusion-induced albumin leakage is tightly coupled to the adherence and emigration of leukocytes in postcapillary venules. This adhesion-dependent injury response is primarily mediated by CD11b/CD18 on activated neutrophils and ICAM-1 on venular endothelium and appears to require L-selectin-dependent leukocyte rolling.
I Kurose; D C Anderson; M Miyasaka; T Tamatani; J C Paulson; R F Todd; J R Rusche; D N Granger
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  74     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-02-28     Completed Date:  1994-02-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  336-43     Citation Subset:  IM    
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130-3932.
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MeSH Terms
Antigens, CD / physiology
Antigens, CD18
Capillary Permeability*
Cell Adhesion
Cell Adhesion Molecules / physiology
Cell Movement
Leukocytes / physiology*
Macrophage-1 Antigen / physiology
Rats, Sprague-Dawley
Reperfusion Injury / pathology,  physiopathology*
Serum Albumin / metabolism*
Splanchnic Circulation*
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD18; 0/Cell Adhesion Molecules; 0/Macrophage-1 Antigen; 0/Serum Albumin; 126880-86-2/L-Selectin

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