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Am J Physiol Heart Circ Physiol (January 8, 2004). doi:10.1152/ajpheart.01000.2003
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Submitted on October 23, 2003
Accepted on January 5, 2004

Leukocyte-dependency of platelet adhesion in postcapillary venules

Dianne Cooper1, Janice Russell1, Keith D. Chitman1, Matthew C. Williams1, Robert E. Wolf2, and D Neil Granger1*

1 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
2 Center of Excellence in Arthritis Rheumatology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

* To whom correspondence should be addressed. E-mail: dgrang{at}lsuhsc.edu.

Reperfusion of ischemic tissues results in development of a pro-inflammatory, prothrombogenic phenotype, culminating in the recruitment of leukocytes and platelets within postcapillary venules. Recent studies have indicated an inter-dependency of platelet and leukocyte adhesion, suggesting that heterotypic blood cell interactions may account for post-ischemic platelet recruitment. The objectives of this study were to: 1) determine whether ischemia/reperfusion (I/R)-induced platelet recruitment is leukocyte-dependent and 2) quantify the contributions of leukocytes and endothelial cells in this platelet recruitment. Intravital microscopy was used to monitor the recruitment of fluorescently-labeled platelets in post-capillary venules of the small intestine after 45min ischemia and 4h reperfusion. To assess the leukocyte-dependency of platelet adhesion, platelets from wild-type mice were infused into mice deficient in neutrophils and/or lymphocytes and mice deficient in key leukocyte adhesion molecules (CD18 and ICAM-1). These anti-leukocyte strategies resulted in significantly reduced platelet recruitment. Simultaneous visualization of platelets and leukocytes enabled quantification of leukocyte-dependent and endothelium-dependent platelet adhesion. It was observed, that in wild-type animals, 74% of I/R-induced platelet adhesion was a result of plateletleukocyte interactions. While the majority of adherent platelets were associated with leukocytes, less than 50% of adherent leukocytes were platelet-bearing, suggesting not all adherent leukocytes support platelet adhesion. These results are consistent with leukocytes playing a major role in supporting I/Rinduced platelet adhesion.




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