This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/8/1491    most recent ATVBAHA.108.167601v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Bournazos, S. Articles by Dransfield, I. PubMed PubMed Citation Articles by Bournazos, S. Articles by Dransfield, I.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1491.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Monocyte Functional Responsiveness After PSGL-1–Mediated Platelet Adhesion Is Dependent on Platelet Activation Status

Stylianos Bournazos; Jillian Rennie; Simon P. Hart; Keith A.A. Fox; Ian Dransfield

From the University of Edinburgh/Medical Research Council (MRC) Centre for Inflammation Research (S.B., J.R., S.P.H., I.D.), Queen’s Medical Research Institute, Edinburgh, UK; and the Centre for Cardiovascular Science (S.B., K.A.A.F.), University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, UK.

Correspondence to Ian Dransfield, The University of Edinburgh/MRC Centre for Inflammation Research, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. E-mail i.dransfield{at}ed.ac.uk

Abstract

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.

Methods and 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 1β and tumor necrosis factor , 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-B 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.

We investigated the functional consequences of P-selectin–dependent adhesion of minimally activated and thrombin-activated platelets to monocytes in terms of cell surface receptor expression, cytokine production, NF-B activation, and engagement of apoptotic programs. Our data clearly suggest that platelet–monocyte interactions may represent a physiological process with little impact on monocyte behavior.

Key Words: monocyte • platelet • adhesion • selectin • thrombin • proinflammatory