Pathways of Complement Activation Following Intestinal Ischemia-Reperfusion in Macaque

Abstract

Pathways of Complement Activation Following Intestinal Ischemia-Reperfusion in MacaqueComplement activation is a key component in the inflammation cascade. In the present study, intestinal ischemia-reperfusion (IIR) was introduced to macaques, and the pathways of complement activation in the multiple organ dysfunction syndrome (MODS) following IIR were investigated, which may provide evidence on the mechanisms underlying the endogenous protection in systemic inflammatory response. IIR was performed by clamping superior mesenteric artery and releasing clamp in 5 macaques. Immunization rate nephelometry and CH50 total complement detection were employed to measure the serum concentration of C3, C4, C-reactive protein (CRP) and total complements. Immunocytochemistry was carried out to detect the contents of IL-1 and NF-κB in polymorphonuclear cells (PMN). Flow cytometry was done to measure the apoptosis rate of PMN. At 24 h after IIR, the amount of total complement (106.6±18.07 U/mL) was reduced to 62.1±9.52 U/mL (p<0.05). In addition, the C3 was reduced by 30% (p<0.05) but C4 remained unchanged after IIR (0.1342±0.07 vs 0.1420±0.06, P>0.05). The apoptosis rate (15.4%±1.14%) of PMN was markedly reduced (3.5%±0.53%) following IIR (p<0.05) accompanied by increased contents of IL-1 and NF-κB. Moreover, CRP was also significantly elevated after IIR (4.33±1.13 mg/L vs 17.73±0.86 mg/L; p<0.01). Following IIR, complements are activated through the alternative pathway. Complement activation fragments can inhibit the apoptosis of PMN and elevate the expressions of acute phase inflammatory proteins including CRP and IL-1, which promotes the inflammation cascade and facilitates the occurrence of MODS.