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Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932
The influence of reductions in venular shear
rate on platelet-endothelial (P/E) cell adhesion has not been
previously addressed. The objectives of this study were to define the
effects of reductions in venular shear rate on P/E cell adhesion and to
determine the interdependence of P/E cell adhesion and
leukocyte-endothelial (L/E) cell adhesion at low shear rates.
Intravital videomicroscopy was used to quantify P/E and L/E cell
adhesion in rat mesenteric venules exposed to shear rates ranging
between 118 ± 9 and 835 ± 44 s
1. Shear rate
was altered in postcapillary venules by rapid, graded blood withdrawal,
without retransfusion of shed blood. Reducing shear rate from >600
s1 to <200 s1 resulted in an eightfold
increase in L/E cell adhesion, whereas P/E cell adhesion increased
18-fold. A blocking antibody directed against P-selectin blunted both
the P/E and L/E cell adhesion elicited by low shear rates.
Immunoneutralization of CD11/CD18 on leukocytes or rendering animals
neutropenic also blocked the shear rate-dependent recruitment of both
platelets and leukocytes. These findings indicate that 1)
low shear rates promote P/E and L/E cell adhesion 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.
P-selectin; neutrophils; CD18; ischemia
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