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 (βS) mice and their wild-type (WT) counterparts (C57B1/6) 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, βS, and chimeric mice produced by transplanting bone marrow from WT or βS mice into WT or P-selectin-deficient (P-sel-/-) mice. Platelet and leukocyte adhesion to endothelial cells in both unstimulated and posthypoxic β S mice were significantly elevated over WT levels. Chimeric mice involving bone marrow transfer from βS mice to P-sel -/- mice exhibited a profound attenuation of both platelet and leukocyte adhesion compared with βS bone marrow transfer to WT mice. These findings indicate that βS mice assume both an inflammatory and prothrombogenic phenotype, with endothelial cell P-selectin playing a major role in mediating these microvascular responses.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||5 55-5|
|State||Published - May 2004|
- Bone marrow transplant