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This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/H1608    most recent 01056.2003v2 01056.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Wood, K. C. Articles by Granger, D. N. Search for Related Content PubMed PubMed Citation Articles by Wood, K. C. Articles by Granger, D. N.

Endothelial cell P-selectin mediates a proinflammatory and prothrombogenic phenotype in cerebral venules of sickle cell transgenic mice

¹Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130; and ²Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Submitted 5 November 2003 ; accepted in final form 22 December 2003

Whereas the adhesion of leukocytes and erythrocytes to vascular endothelium has been implicated in the vasooclusive events associated with sickle cell disease, the role of platelet-vessel wall interactions in this process remains undefined. The objectives of this study were to: 1) determine whether the adhesion of platelets and leukocytes in cerebral venules differs between sickle cell transgenic (^S) mice and their wild-type (WT) counterparts (C57Bl/6) under both resting and posthypoxic conditions, and 2) define the contributions of P-selectin to these adhesion processes. Animals were anesthetized, and platelet and leukocyte interactions with endothelial cells of cerebral postcapillary venules were monitored and quantified using intravital fluorescence microscopy in WT, ^S, and chimeric mice produced by transplanting bone marrow from WT or ^S mice into WT or P-selectin-deficient (P-sel^–/–) mice. Platelet and leukocyte adhesion to endothelial cells in both unstimulated and posthypoxic ^S mice were significantly elevated over WT levels. Chimeric mice involving bone marrow transfer from ^S mice to P-sel^–/– mice exhibited a profound attenuation of both platelet and leukocyte adhesion compared with ^S bone marrow transfer to WT mice. These findings indicate that ^S mice assume both an inflammatory and prothrombogenic phenotype, with endothelial cell P-selectin playing a major role in mediating these microvascular responses.

platelet; leukocyte; brain; bone marrow transplant