Protective effect of C5a receptor 1 antagonist on ascending urinary tract infection in mice

Abstract

Objective To investigate the protective effect of complement 5a receptor 1 (C5aR1) antagonist on ascending urinary tract infection in mice. Methods (1) Female C57BL/6 mice were randomly divided into experimental and control groups: 38 mice in each group, and inoculated with E. coli by urethral catheterization to set up the ascending urinary tract infection model. C5aR1 antagonist (W54011 or PMX53) and corresponding control (PBS or control peptide) were initially given either at 2 h before or 3 h after infection by intraperitoneal injection. Mice were sacrificed to assess the infection in bladder and kidney at 24 or 48 h after infection. The bacterial load of bladder and kidney tissue was measured by agar plate assay. The mRNA expression of renal inflammatory factors was detected by real-time RCR. The renal tissue injury and inflammatory cell infiltration were assessed by HE staining and pathological scores. (2) Primary cultured renal tubular epithelial cells were randomly divided into antagonist and control groups to detect and compare the bacterial adhesion to renal tubular epithelial cells in vitro. Results Compared with control groups, the initial delivery of C5aR1 antagonist (W54011 or PMX53) before E.coli inoculation reduced the bacterial load in bladder and kidney tissue 48 h after infection (all P<0.01). In experimental group given W54011 before infection, the renal pathological scores were reduced (both P<0.05), as well as renal inflammatory factor expressions: CXCL-1 mRNA, IL-6 mRNA and TNF-α mRNA (all P<0.05). Compared with corresponding control groups, the initial delivery of PMX53 after E. coli inoculation could also reduce the bacterial load in bladder and kidney tissue 48 h after infection (both P<0.01). Furthermore, C5aR1 antagonists W54011 and PMX53 could decrease bacteria adhesion to renal tubular epithelial cells in vitro, compared with control groups (both P<0.05). Conclusions C5aR1 antagonists can significantly attenuate renal tissue injury, ameliorate renal inflammation and the adhesion of bacteria to renal epithelial cells. C5aR1 may be an effective target for the prevention and treatment of urinary tract infection. Key words: Urinary tract infections; Complement 5a; Epithelial cell; Kidney tubules; C5aR1 antagonist