A monoclonal antibody to a 67 kD cell membrane glycoprotein directly induces persistent platelet aggregation independently of granule secretion.
The transition from reversible to persistent platelet aggregation has been difficult to study because of interference both from preceding primary aggregation and from the events associated with granule secretion during secondary aggregation. As a result it remains unclear whether the persistence of aggregation involves some secretion-independent specific platelet surface reactions. Here we show that a monoclonal antibody (MAb), LeoAl, against a newly described 67 kD platelet membrane glycoprotein induced active platelet aggregation consisting of two distinct phases. The first secretion-independent phase was in several respects (extracellular protein, divalent cation, and pH dependence) different from primary aggregation, but closely resembled the transition from primary to secondary aggregation observed at certain concentrations of physiological agonists. The second, faster phase was indistinguishable from secretion-dependent aggregation to various stimulants. It was shown that p67, GPIIb-IIIa and FC gamma RII are all involved in the observed aggregation, probably through their close topographical association. It is suggested that LeoAl-induced aggregation can be used as a model to study the receptors, ligands and metabolic pathways specifically involved in the transition from reversible to persistent platelet aggregation.
Zuzel
M
M
Department of Haematology, Royal Liverpool Hospital.
Walton
S
S
Burns
G F
GF
Berndt
M C
MC
Cawley
J C
JC
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D010974:Platelet Aggregation / Q000276:immunology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG