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Specific accumulation of circulating monocytes and polymorphonuclear
leukocytes on platelet thrombi in a vascular injury model
D Kirchhofer, MA Riederer and HR Baumgartner
F. Hoffmann-La Roche Ltd, Pharma Division, Preclinical Research, Basel,
Switzerland.
The adhesion of leukocytes to platelets deposited at the site of vascular
injury may represent an important mechanism by which leukocytes contribute
to hemostasis and thrombosis. In this study, we examined whether, in
comparison with their distribution in circulating blood, certain leukocyte
types are enriched at sites of platelet deposition. We used an experimental
vascular injury model, in which human fibrillar collagen was exposed to
anticoagulated human whole blood flowing through parallel-plate chambers
(venous shear rate, 65/s). The platelet-adherent leukocytes were detached
by EDTA treatment and analyzed by flow cytometry using cell-type-specific
antibodies. The predominant leukocytes found in platelet thrombi were
polymorphonuclear leukocytes, accounting for 76% of bound leukocytes (62%
in circulating blood), whereas T and B lymphocytes did not significantly
accumulate on thrombi, comprising a fraction of less than 5% (32% in
circulating blood). Monocytes constituted 16% of platelet thrombus-bound
leukocytes, which represents an almost fourfold enrichment as compared with
their proportion in circulating blood. Almost identical results were
obtained when we analyzed leukocytes adhering to platelet monolayers, which
were formed by blocking glycoprotein IIb-IIIa, thus preventing platelet
aggregation on top of the collagen-adherent platelets. Furthermore,
leukocyte adhesion to platelet monolayers was completely inhibited by an
anti-P-selectin antibody (50% inhibitory concentration, 0.3 microg/mL),
whereas it reached a plateau at about 70% inhibition on platelet thrombi.
This difference could be explained by a possible function of glycoprotein
IIb-IIIa in leukocyte immobilization to thrombi or by the high local
concentration of P- selectin in the growing thrombi. The results suggest
that, because of their known abilities to promote coagulation and
thrombolysis, the monocytes and polymorphonuclear leukocytes accumulating
on forming platelet thrombi could play an important role in modulating
thrombotic and hemostatic processes.
Volume 89,
Issue 4,
pp. 1270-1278,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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