HUMAN LAMININ PRODUCES HUMAN PLATELET-AGGREGATION IN-VITRO

The effects of laminin isoforms on platelet aggregation were compared and characterized in platelet rich plasma (PRP) obtained from 26 healt hy human volunteers. In approximately 38% of the individuals tested, h uman laminin produced a biphasic platelet aggregation response. Human laminin produced only a primary phase in the remaining ''non-responsiv e'' individuals. Mouse laminin, rat laminin and human merosin did not cause platelet aggregation in any of the volunteers. The biphasic plat elet aggregation response caused by human laminin was concentration-de pendent (0.3-30 nM) and was consistently observed upon repeated testin g of ''responsive'' individuals. The secondary phase of aggregation pr oduced by human laminin in ''responsive'' individuals was abolished by aspirin, SQ 29,548, a selective thromboxane antagonist, and SK&F 1067 60, an RGD-derived platelet fibrinogen receptor (GPIIb/IIIa) antagonis t. Also, the secondary phase of aggregation was not observed in washed platelets. Both the primary and secondary platelet responses produced by human laminin were abolished by a VLA-6 (alpha(6) beta(1)) monoclo nal antibody, but not by the YIGSR pentapeptide. In conclusion, human laminin causes thromboxane-dependent platelet aggregation, in vitro, i n a significant population of human volunteers. The aggregation respon se was dependent upon the interaction of human laminin with platelet V LA-6 (alpha(6) beta(1)>). These novel results suggest that in some ind ividuals laminin may play an important role in hemostasis and thrombog enesis.