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 atherosclerotic (A.S.-) lesion is one of the key events in early atherogenesis. Using a flow model for the damaged vessel wall, we examined the ability of ECM-bound platelets to induce monocyte tethering and adhesion. Whereas ECM-proteins alone induced monocyte adhesion only at low shear stresses (< 100 mPa), ECM-bound platelets induced monocyte rolling and adhesion at shear stresses up to 240 mPa. Studies with specific antibodies showed that monocyte adhesion to platelets was mainly mediated by P-selectin and monocyte PSGL-1 (maximum inhibition 90%). beta2-Integrin blocking CD18 and CD11b antibodies partly inhibited the arrest of rolling cells. Antibodies against other adhesion molecules such as LFA-1, PECAM-1, and beta1-integrins had no effect. Even sparsely adhered platelets (approximately 10% coverage of the surface) already strongly supported monocyte tethering. In conclusion, activated platelets present on ECM are a powerful adhesive substrate for monocyte recruitment under flow conditions.
Kuijper
P H
PH
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands. P.Kuijper@hli.azu.nl
Gallardo Torres
H I
HI
Houben
L A
LA
Lammers
J W
JW
Zwaginga
J J
JJ
Koenderman
L
L
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D013314:Stress, Mechanical
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D019007:P-Selectin