Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 7, Issue 1, Pages 143-151Publisher
WILEY
DOI: 10.1111/j.1538-7836.2008.03170.x
Keywords
collagen; monocytes; PECAM-1; platelets
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Funding
- University Paris 7
- Leducq Foundation
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Background: Blood vessel damage results in exposure of the subendothelial matrix, to which platelets adhere. Monocytes are recruited and activated at the site of injury. Objectives: Here we studied the effect of monocytes on platelet activation induced by exposure to fibrillar collagen. Methods: Washed platelets and isolated monocytes (100/1) were coincubated with type I collagen in static adhesion conditions or in suspension. Platelet activation was assessed by measuring RANTES production and alpha-granule secretion. Platelet adherence on immobilized collagen was analyzed by fluorescence confocal microscopy. Cell-cell contacts were prevented by incubating platelets and monocytes in transwell coculture dishes. Experiments were also performed in the presence of soluble recombinant platelet endothelial cell adhesion molecule-1 (PECAM-1) or of antibodies to PECAM-1. Results: Unexpectedly, unstimulated monocytes limited the initial phase of platelet activation by fibrillar collagen. In adhesion conditions, monocytes reduced the secretion by platelets of the inflammatory chemokine RANTES and of beta-thromboglobulin and the formation of platelet aggregates. The inhibitory effect of monocytes on platelet activation required direct cell-cell contacts between platelets and monocytes. Monocytes also inhibited collagen-induced platelet activation in suspension conditions as assessed by the reduction of P-selectin exposure and RANTES secretion. A recovery of platelet responses was observed in the presence of soluble PECAM-1 and of PECAM-1.3 Fab, indicating that PECAM-1 is involved in monocyte-triggered downregulation of platelet reactivity. Conclusions: Our data provide the first evidence that unstimulated monocytes limit the initial phase of platelet activation by collagen via a mechanism that is, at least in part, PECAM-1-dependent.
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