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Am J Physiol Gastrointest Liver Physiol (September 11, 2002). doi:10.1152/ajpgi.00303.2002
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Articles in PresS, published online ahead of print September 11, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00303.2002
Submitted on July 25, 2002
Accepted on September 9, 2002

Low Venular Shear Rates Promote Leukocyte-Dependent Recruitment of Adherent Platelets

Janice Russell1, Dianne Cooper1, Anitaben Tailor1, Karen Y. Stokes1, and D. N. Granger1*

1 Department of Molecular and Cellular Physiology, Louisiana State University, Shreveport, LA, USA

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

Although it is known that low shear rates in postcapillary venules enhance the recruitment of adherent leukocytes, the influence of reductions in venular shear rate on platelet-endothelial cell (P/E) adhesion has not been previously addressed. The objectives of this study were to 1) define the effects of reductions in venular shear rate on P/E adhesion, 2) determine whether shear rate-induced P/E adhesion affects (or is affected by) the corresponding recruitment of adherent leukocytes (L/E adhesion), and 3) estimate the contribution of reduced shear rate to the platelet and leukocyte adhesion seen in venules exposed to ischemia-reperfusion (I/R). Intravital videomicroscopy was used to quantify P/E and L/E adhesion in rat mesenteric venules exposed to shear rates ranging between 118 ± 9 and 835 ± 44 sec-1. Shear rate was altered in postcapillary venules by rapid, graded blood withdrawal, without retransfusion of shed blood. Reducing shear rate from >600 sec-1 to <200 sec-1 resulted in an 8-fold increase (p<0.01) in L/E adhesion, while P/E adhesion increased 18-fold (p<0.01). A blocking antibody directed against P-selectin significantly blunted both the P/E and L/E adhesion elicited by low shear rates. Immunoneutralization of the leukocyte adhesion molecule CD11/CD18 or rendering animals neutropenic with antineutrophil serum (ANS) also blocked the shear rate-dependent recruitment of both platelets and leukocytes. These findings indicate that 1) low shear rates promote the recruitment of adherent platelets and leukocytes in mesenteric venules, and 2) adherent neutrophils (mediated by CD11/CD18) create a platform onto which platelets can bind to the venular wall at low shear rates.




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