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 healthy human volunteers. In approximately 38% of the individuals tested, human laminin produced a biphasic platelet aggregation response. Human laminin produced only a primary phase in the remaining ''non-responsive'' individuals. Mouse laminin, rat laminin and human merosin did not cause platelet aggregation in any of the volunteers. The biphasic platelet aggregation response caused by human laminin was concentration-dependent (0.3-30 nM) and was consistently observed upon repeated testing of ''responsive'' individuals. The secondary phase of aggregation produced by human laminin in ''responsive'' individuals was abolished by aspirin, SQ 29,548, a selective thromboxane antagonist, and SK&F 106760, an RGD-derived platelet fibrinogen receptor (GPIIb/IIIa) antagonist. 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)) monoclonal antibody, but not by the YIGSR pentapeptide. In conclusion, human laminin causes thromboxane-dependent platelet aggregation, in vitro, in a significant population of human volunteers. The aggregation response was dependent upon the interaction of human laminin with platelet VLA-6 (alpha(6) beta(1)>). These novel results suggest that in some individuals laminin may play an important role in hemostasis and thrombogenesis.