COLLAGEN-TARGETED ANTIBODIES INHIBIT PLATELET-DEPENDENT THROMBOSIS IN-VIVO

Subendothelial collagen is one of the main triggers of platelet-depend ent thrombus formation in arteries. The antithrombotic effects of rabb it polyclonal inhibitory antibodies to rat collagen type I-III and of murine non-inhibitory monoclonals to human recombinant single-/two-cha in urokinase-type plasminogen activator (rscu-/rtcu-PA), cross-reactin g with rat scu-/tcu-PA and their chemically synthesized conjugate, wer e studied both in vitro and in vivo. Anticollagen antibodies and bispe cific conjugate inhibited human platelet adhesion, aggregation and for mation of thrombus-like structures induced by rat collagen immobilized on the polystyrene surface in a condition mimicing a high shear rates in the large elastic arteries. Monoclonals to human rscu-/rtcu-PA did not block the collagen-induced platelet activation in vitro. The shor t-term treatment of the collagen-soaked silk thread by the collagen an tibodies suppressed the platelet-dependent thrombus formation in the a rterio-venous shunt in rats by 56 +/- 4% (P<0.05). Bispecific conjugat e, directed to collagen and endogenous rat scu/tcu-PA (1)inhibited thr ombus formation by the same factor as anticollagen antibodies. The tre atment of collagen-adsorbed conjugate by human rtcu-PA did not increas e the antithrombotic effect. The present results suggest, that the loc al administration of the anticollagen antibodies to the site of vascul ar injury can be an efficient tool for prophylaxis of platelet-depende nt thrombus formation in arteries at thrombolysis or percutaneous tran sluminal coronary angioplasty.