Bacterial infections in coagulating blood: calcium inhibits complement alternative pathway

摘要

Bacterial survival in coagulated blood can cause complications associated with endocarditis or biomaterial infections. We report that during recalcification of diluted (1:5) citrated human whole blood, the killing activity toward E. coli decreased 90-fold after the addition of thrombin (1 U/ml) and CaCl{sub}2 (50 mM). The killing activity in diluted citrated whole blood or plasma was Mg{sup}(2+)-dependent and Ca{sup}(2+)-independent (as well as heat-inactivated in plasma), demonstrating complementalternative pathway mediation of E. coli lysis. Addition of calcium from 0 to 10 mM CaCl{sub}2 in the presence of heparin (5 U/ml), PPACK (250μM), or hirudin (33 U/ml) to diluted citrated whole blood or plasma caused a dose-dependent inhibition ofbacterial killing. Excess addition of fibrin or fibrinogen had no effect on bacterial survival in whole blood or plasma, with or without coagulation. Physiological levels of Ca{sup}(2+) (1 mM) had a cytoprotective effect that attenuated alternativepathway killing of E. coli. This previously unrecognized calcium modulation of the alternative pathway killing must be considered in the study of bacterial survival in coagulating blood.