Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG.
The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding.
Ryu
T
T
Department of Medicine, Michigan State University, East Lansing, MI 48824.
Davis
J M
JM
Schwartz
K A
KA
D000255:Adenosine Triphosphate / Q000097:blood; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology*; D007457:Iodine Radioisotopes; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D011233:Precipitin Tests; D011696:Purpura, Thrombocytopenic / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D010975:Platelet Aggregation Inhibitors; D000255:Adenosine Triphosphate; D005340:Fibrinogen