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.
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
R N
RN
Willette
B L
BL
Storer
R K
RK
Clark
E H
EH
Ohlstein
D000328:Adult; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D016029:Receptors, Very Late Antigen / Q000502:physiology
D007797:Laminin; D010456:Peptides, Cyclic; D016029:Receptors, Very Late Antigen; C071275:SK&F 106760