Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG
- Michigan State Univ., East Lansing (USA)
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.
- OSTI ID:
- 6530206
- Journal Information:
- Journal of Laboratory and Clinical Medicine; (USA), Vol. 116:1; ISSN 0022-2143
- Country of Publication:
- United States
- Language:
- English
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BLOOD PLATELETS
BIOLOGICAL FUNCTIONS
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PATHOGENESIS
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DOSE-RESPONSE RELATIONSHIPS
FIBRINOGEN
IMMUNOGLOBULINS
IODINE 125
RADIOASSAY
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
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BLOOD COAGULATION FACTORS
BODY FLUIDS
CARDIOVASCULAR DISEASES
COAGULANTS
DAYS LIVING RADIOISOTOPES
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FUNCTIONS
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
INTERMEDIATE MASS NUCLEI
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NUCLEI
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ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
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550201* - Biochemistry- Tracer Techniques