Mechanism by which complement proteins C5b-9 increase platelet prothrombinase activity

Journal Article · Wed Nov 05 04:00:00 EST 1986 · J. Biol. Chem.; (United States)

OSTI ID:7090844

Wiedmer, T; Esmon, C T; Sims, P J

Membrane assembly of complement proteins C5b-9 on human platelets results in a dose-dependent increase in the binding of coagulation factors Va and Xa to the plasma membrane, concomitant with a marked increase in platelet prothrombinase activity. Factor Va binding increased by 6-15-fold in platelets treated with the C5b-9 proteins as compared to controls. In the presence of near-saturating concentrations of factor Xa, factor Va binding to C5b-9-treated platelets approximately doubled. In the absence of added factor Va, C5b-9-treated platelets bound 1700 molecules of factor Xa versus 50 molecules/cell bound to controls, suggesting that C5b-9 assembly on the platelet surface initiates the release of platelet factor V from the ..cap alpha..-granules. The capacity of the C5b-9 proteins to initiate the nonolytic release of the platelet ..cap alpha..-granule storage pool was confirmed by assay for platelet factor 4. When measured in the presence of exogenous factor Va (2 ..mu..g/ml), factor Xa uptake by C5b-9 platelets increased to approximately 5500 molecules/cell (versus 330 molecules/cell for controls). Removal of external Ca/sup 2 +/ inhibited the C5b-9-initiated release of the ..cap alpha..-granule storage pool and reduced by approximately 50% the expression of new factor Va binding sites, suggesting that these two events contributing to increased platelet prothrombinase activity are mediated in part by the influx of Ca/sup 2 +/ across the C5b-9 pore.

• Research Organization: Oklahoma Blood Institute, Oklahoma City
• OSTI ID: 7090844
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 261:31; ISSN JBCHA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALBUMINS
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
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