The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through glycoprotein IIb-IIIa.
The secretory and aggregation responses of stirred platelets exposed to complement proteins C5b-9 was investigated. C5b-9 assembly on the platelet surface resulted in the release of dense granule adenosine triphosphate (ATP) accompanied by a decrease in sample turbidity, but no detectable cell lysis. Inhibition of cellular protein kinase C completely blocked the C5b-9 initiated release of ATP, confirming the secretory nature of this response. Addition of fibrinogen (up to 1 mg/mL) had no effect on either the release of ATP or the decreased turbidity observed for C5b-9 cells. Addition of the peptides Arg-Gly-Asp-Ser (RGDS) and fibrinogen gamma-chain carboxyl-terminal (gamma 397-411) at concentrations sufficient to completely block fibrinogen binding to GP IIb-IIIa had no effect on either C5b-9 induced dense granule secretion or the associated turbidity change. Microscopic examination and electronic particle counting of the stirred platelet suspensions confirmed that no aggregation of C5b-9 platelets occurred even when these cells were stirred in the presence of fibrinogen. The capacity of the C5b-9 proteins to initiate platelet secretion without activation of cell surface glycoprotein (GP) IIb-IIIa suggests a mechanism for intravascular dissemination of activated platelets during complement activation in vivo.
Ando
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B
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Wiedmer
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T
Sims
P J
PJ
D000244:Adenosine Diphosphate / Q000502:physiology; D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D012542:Scattering, Radiation
D015938:Complement Membrane Attack Complex; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003165:Complement System Proteins