Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses.
Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb-induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.
Jennings
L K
LK
Phillips
D R
DR
Walker
W S
WS
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001791:Blood Platelet Disorders / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D012701:Serotonin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D012701:Serotonin; D002118:Calcium