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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1317-1323
Leukocyte-leukocyte interactions mediated by platelet
microparticles under flow
Stephen B. Forlow,
Rodger P. McEver, and
Matthias
U. Nollert
From the School of Chemical Engineering and Materials Science,
University of Oklahoma, Norman, Oklahoma; the W. K. Warren Medical
Research Institute, Departments of Medicine and Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center,
Oklahoma City, Oklahoma; and the Cardiovascular Biology Research
Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
Platelet microparticles (PMPs) are released from activated platelets
and express functional adhesion receptors, including P-selectin, on
their surface. PMP concentrations are elevated in many disorders, and
their role in accelerating coagulation has been studied. However, their
role in leukocyte aggregation has not been defined. We hypothesized
that P-selectin-expressing PMPs bridge leukocytes that express
P-selectin glycoprotein ligand-1 (PSGL-1), thereby allowing them to
interact under flow conditions. PMPs were isolated from platelet-rich
plasma or were generated by activating washed platelets with calcium
ionophore. PMPs increased transient adhesion of flowing
HL-60 cells or neutrophils to HL-60 cells or neutrophils
prebound to the surface of a parallel plate flow chamber. Homotypic
neutrophil interactions are initiated by the binding of L-selectin to
PSGL-1. However, even when L-selectin function was blocked, PMPs
allowed flowing neutrophils to aggregate and to interact with
PSGL-1-expressing cells prebound to the surface of the flow chamber.
The microparticle-mediated cell interactions occurred at lower shear
stresses than those mediated by L-selectin. PMPs may enhance
leukocyte aggregation and leukocyte accumulation on selectin-expressing
substrates, especially in diseases where the concentration of the
particles is elevated.
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