Effects of various inhibitors on platelet activation induced by TP 82, a CD 9 monoclonal antibody.
TP 82, a monoclonal antibody against CD 9 antigen, induced human platelet activation at concentrations higher than 0.4 microgram/mL in terms of aggregation, release of intracellular granule contents, production of arachidonic acid metabolites, and elevation of the intracellular Ca2+ concentration. The effects of a competitive inhibitor of ADP, acetylsalicylic acid, EGTA, and GRGDSP which blocks fibrinogen binding to IIb/IIIa complex suggested that each of released ADP, thromboxane A2, extracellular Ca2+, and close cell contact acts together to potentiate platelet activation induced by TP 82. While each of these inhibitors severely suppressed platelet activation induced by lower concentrations of the antibody (less than or equal to 0.8 microgram/mL), that induced by higher concentrations (greater than or equal to 3.2 micrograms/mL) was only partially blocked. Intracellular Ca2+ elevation was totally dependent upon the production of thromboxane A2, regardless of the antibody concentrations.
Ozaki
Y
Y
Department of Clinical and Laboratory Medicine, Yamanashi Medical College, Nakakomma, Japan.
Matsumoto
Y
Y
Yatomi
Y
Y
Higashihara
M
M
Kariya
T
T
Kume
S
S
D000244:Adenosine Diphosphate / Q000378:metabolism; D000331:Aequorin / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D060245:Tetraspanin 29; D013928:Thromboxane A2 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001095:Arachidonic Acids; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D060245:Tetraspanin 29; D016718:Arachidonic Acid; D012701:Serotonin; D000331:Aequorin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; D001241:Aspirin; D002118:Calcium