P-SELECTIN AND MAC-1 MEDIATE MONOCYTE ROLLING AND ADHESION TO ECM-BOUND PLATELETS UNDER FLOW CONDITIONS

Accumulation of monocyte-derived foam cells in focal areas of the athe rosclerotic (A.S.-) lesion is one of the key events in early atherogen esis. Using a flow model for the damaged vessel wall, we examined the ability of ECM-bound platelets to induce monocyte tethering and adhesi on. Whereas ECM-proteins alone induced monocyte adhesion only at low s hear stresses (<100 mPa), ECM-bound platelets induced monocyte rolling and adhesion at shear stresses up to 240 mPa. Studies with specific a ntibodies showed that monocyte adhesion to platelets was mainly mediat ed by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). beta(2) -Integrin blocking CD18 and CD11b antibodies partly inhibited the arre st of rolling cells. Antibodies against other adhesion molecules such as LFA-1, PECAM-1, and beta(1)-integrins had no effect. Even sparsely adhered platelets (similar to 10% coverage of the surface) already str ongly supported monocyte tethering. In conclusion, activated platelets present on ECM are a powerful adhesive substrate for monocyte recruit ment under flow conditions.