Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes

Abstract

Background: Activated platelets exert a pro-inflammatory action that can be largely ascribed to their ability to interact with leukocytes and modulate their activity. We hypothesized that platelet activation and consequent formation of monocyte-platelet aggregates (MPA) induces a pro-inflammatory phenotype in circulating monocytes. Methodology/Principal Findings: CD62P + platelets and MPA were measured, and monocytes characterized, by whole blood flow cytometry in healthy subjects, before and two days after receiving influenza immunization. Three monocytic subsets were identified: CD14 +CD16 -, CD14 highCD16 +and CD14 lowCD16 +. The increase in high sensitivity C-reactive protein post-immunization was accompanied by increased platelet activation and MPA formation (25.02±12.57 vs 41.48±16.81; p = 0.01), along with enhancement of circulating CD14 highCD16 + cells (4.7±3.6 vs 10.4±4.8; p = 0.003), their percentage being linearly related to levels of CD62P +-platelets (r 2 = 0.4347; p = 0.0008). In separate in vitro experiments, co-incubation of CD14 +CD16 - cells, isolated from healthy donor subjects, with autologous platelets gave rise to up-regulation of CD16 on monocytes as compared with those maintained in medium alone (% change in CD14 +CD16 + cells following 48 h co-incubation of monocytes with platelets was +106±51% vs monocytes in medium alone; p&0.001). This effect correlated directly with degree of MPA formation (r 2 = 0.7731; p&0.0001) and was associated with increased monocyte adhesion to endothelial cells. P-selectin glycoprotein ligand-1 (PSGL-1) blocking antibody, which abrogates MPA formation, abolished these effects, as did the cyclooxygenase (COX)-2 selective inhibitor NS-398, aspirin and the EP1/EP2-selective antagonist AH6809. Conclusions/Significance: These data suggest that MPA formation, as occurs in the blood under pro-inflammatory conditions, expands the pool of circulating CD14 highCD16 + monocytes in a COX-2 dependent manner, and these monocytes exhibit increased adhesion to endothelium. Our findings delineate a novel mechanism underlying the pro-inflammatory effect of platelet activation. © 2011 Passacquale et al.