Differential role of von Willebrand factor and P-selectin on microvascular thrombosis in endotoxemia.
OBJECTIVE
Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet-microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia.


RESULTS
A light/dye-induced thrombosis model was used in cremaster microvessels of saline or LPS-injected mice (wild-type, P-selectin-deficient, vWF-deficient, or littermate controls). In each strain except vWF-deficient mice, LPS enhanced thrombosis in venules, resulting in approximately 30% to 55% reduction in times to thrombotic occlusion. LPS had no effect on thrombosis in vWF-deficient mice, although these mice had similar systemic responses to LPS (tachycardia, thrombocytopenia, and plasma coagulation markers). vWF-deficient mice demonstrated prolonged times to thrombotic occlusion relative to littermates. LPS increased plasma vWF in each strain studied. While immunofluorescence in wild-type mice failed to detect LPS-induced differences in microvascular vWF expression, it revealed markedly higher vWF expression in venules relative to arterioles.


CONCLUSIONS
vWF mediates light/dye-induced microvascular thrombosis and endotoxin-induced enhancement of thrombosis in mouse cremaster venules; P-selectin is not required for enhanced thrombosis in response to endotoxin. Enhanced vWF expression in venules relative to arterioles has potential implications for the differences in thrombotic responses among these microvessels.
Patel
Kavita N
KN
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Soubra
Said H
SH
Medical Care Line, Michael E. DeBakey VA Medical Center, Houston, TX 77030.|Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Bellera
Ricardo V
RV
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Dong
Jing-Fei
JF
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
McMullen
Colleen A
CA
Department of Physiology, University of Kentucky, Lexington, KY 40536.
Burns
Alan R
AR
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.|Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Rumbaut
Rolando E
RE
Medical Care Line, Michael E. DeBakey VA Medical Center, Houston, TX 77030.|Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.|Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D019446:Endotoxemia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000503:physiopathology; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D014699:Venules / Q000187:drug effects / Q000503:physiopathology; D014841:von Willebrand Factor / Q000235:genetics / Q000502:physiology*
D008070:Lipopolysaccharides; D019007:P-Selectin; D014841:von Willebrand Factor
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