Complement initiation and regulation differ by sex in intestinal ischemia reperfusion injury

Abstract

Abstract Males and females frequently sustain distinct symptoms during ischemic events and subsequent inflammatory events. The inflammatory events include significant complement activation, neutrophil infiltration and significant cytokine secretions. The past literature suggests that complement activation may include a sex-linked protein. Therefore, we hypothesized that complement activation may vary by sex during intestinal ischemia/reperfusion (IR) injury. We subjected male and female mice to 30 min intestinal ischemia followed by 15, 30, 60 or 120 min reperfusion. Additional mice of each sex was subjected to sham surgery. Intestinal sections were stained and complement initiation pathways and time points of deposition determined. Complement regulatory molecules were also examined. Initial results suggest that males expressed more C1q compared to females, while females expressed more MBL than males. In addition, complement regulators varied by sex. Our data demonstrate that complement initiation and regulation differ between sexes during intestinal IR. These response differences in intestinal IR provide insight into the sexual dimorphism of ischemic intestine diseases and may aid in the development of sex-specific therapies that reduce intestinal injury.