BIOMECHANICS OF CELL-INTERACTIONS IN SHEAR FIELDS

Cellular interactions play a key role in diverse biological processes within the cardiovascular system. Targeting of leukocytes to sites of inflammation is viewed as a multistage process of sequential involveme nt of distinct adhesion molecules on the leukocyte and endothelial cel l (EC) surface that is dictated by the local fluid dynamic environment . For neutrophils, the initial contact and rolling along the vessel wa ll are mediated primarily by selectins. Subsequent firm adhesion requi res activation of neutrophil beta(2) integrins and binding to their li gand ICAM-1 on the EC surface. The final step of this cascade of event s includes neutrophil transmigration to extravascular tissue space. Th e neutrophil model of emigration in inflammation has been extended and refined to account for monocyte and T cell interactions with ECs. Pla telet adhesion to thrombogenic surfaces (i.e, immobilized von Willebra nd factor) under flow follows the general principles of leukocyte extr avasation. More specifically, platelet glycoprotein (GP) Ib alpha appe ars to mediate an initial selectin-like tethering platelet-vWf interac tion, followed by alpha(II beta)beta(3) integrin activation and firm a dhesion. Some of the signaling mechanisms associated with cellular int eractions in inflammatory and thrombotic processes are discussed. Thes e basic principles are also discussed in the context of tissue enginee ring research. (C) 1998 Elsevier Science B.V.