Synergistic action in platelet activation induced by an antiplatelet autoantibody in ITP.
We detected an autoantibody which activated normal platelets in a patient with immune thrombocytopenic purpura and investigated the mechanism by which this autoantibody mediated platelet activation. The patient's IgG induced platelet aggregation and ATP secretion in normal platelet-rich plasma (PRP). IgG-induced aggregation was inhibited by aspirin (ASA), apyrase, a protein kinase C (PKC) inhibitor and two anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibodies. The increase of aequorin-detected intraplatelet Ca2+ induced by the patient's IgG was extremely slight. Phosphorylation of a 40 kDa protein was induced by the patient's IgG without any obvious phosphorylation of a 20 kDa protein, and was inhibited by a PKC inhibitor but not by ASA. With ASA-treated normal PRP, the patient's IgG failed to induce aggregation itself, but enhanced ADP- or STA2-induced aggregation. Western blotting and immunoprecipitation experiments showed that the patient's IgG reacted to a protein of 36 kDa. These results suggest that the platelet activation induced by this autoantibody depended on both the selective activation of PKC and the slight Ca2+ mobilization induced by thromboxane A2 synthesis, while the aggregation depended on secretion induced by the synergistic action of the above two mechanisms and was mediated through GP IIb/IIIa.
Yanabu
M
M
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Nomura
S
S
Fukuroi
T
T
Soga
T
T
Kondo
K
K
Sone
N
N
Kitada
C
C
Nagata
H
H
Kokawa
T
T
Yasunaga
K
K
D000255:Adenosine Triphosphate / Q000097:blood; D000293:Adolescent; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D011696:Purpura, Thrombocytopenic / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D000255:Adenosine Triphosphate; D002118:Calcium