Exogenous C3 Postpones Complement Exhaustion and Confers Organ Protection in Murine Sepsis

Abstract

Sepsis in human being is a challenging and life-threatening problem. Complement activation is an essential event in sepsis. The present study observed the dynamic levels of complement components in sepsis and evaluated the role of exogenous complement protein in outcomes. The relationship between complement and inflammatory cytokines was also investigated. Colon ascendens stent peritonitis (CASP) surgery was performed in wild-type C57BL/6 mice to induce sepsis. After 6 h of CASP, a single intraperitoneal injection of human purified C3 (HuC3, 1 mg) was carried out, with 200 uL phosphate-buffered saline injection for control purpose. Plasma levels of C3, complement factor H (CFH), and inflammatory cytokines at different time points were detected. Bacterial burden and organ damage were evaluated after 24 h of surgical procedure. The plasma C3 levels began to fall at 6 h post CASP, followed by an irreversible process of consumption. A single injection of HuC3 stabilized C3 levels for about 6 h, decreasing the 24 h mortality from 60% to 20%. Administration of exogenous C3 reduced bacterial burden and attenuated organ injury in sepsis. Plasma levels of CFH and TNF-α were correlated with the depletion of C3. We demonstrated a consumptive depletion of complement components toward septic peritonitis. Exogenous C3 supplementation in early stage of sepsis is helpful to sustain C3 levels, with enhanced bacterial clearance and improved outcomes.