Monocyte functional responsiveness after PSGL-1-mediated platelet adhesion is dependent on platelet activation status.
OBJECTIVE
Acute coronary diseases are characterized by elevated levels of circulating platelet-leukocyte complexes, raising the possibility that proinflammatory processes might be initiated in leukocytes after platelet adhesion. Here we examined the mechanism of platelet binding to polymorphonuclear leukocytes, monocytes, and monocyte subsets and investigated the potential functional consequences of monocyte binding to minimally activated or thrombin-activated platelets.


RESULTS
In this article, we describe key differences in terms of stability of PSGL-1-mediated interaction of platelets with monocytes and polymorphonuclear leukocytes and a small but significant difference in platelet binding to monocyte subsets (CD14(high) and CD14(low)/HLA-DR(high)). We also report differential effects of platelet binding on monocyte functional responses between minimally and thrombin-activated platelets. In particular, monocyte CD11b expression and release of proinflammatory cytokines, like interleukin 1beta and tumor necrosis factor alpha, were significantly upregulated on adhesion of stimulated platelets, whereas unstimulated platelets had no effect. Moreover, binding of unstimulated, but not of thrombin-activated, platelets to monocytes had no impact on NF-kappaB activity, monocyte migration, and induction of apoptosis in the absence of survival factors.


CONCLUSIONS
Our data suggest that in the absence of overt activation, PSGL-1-P-selectin-dependent platelet binding to monocytes represents a normal physiological process with little impact on the potential of monocytes to cause vascular injury.
Bournazos
Stylianos
S
The University of Edinburgh/MRC Centre for Inflammation Research, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Rennie
Jillian
J
Hart
Simon P
SP
Fox
Keith A A
KA
Dransfield
Ian
I
D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010973:Platelet Adhesiveness / Q000502:physiology*
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein