differential role for cd80 and cd86 in the regulation of the innate immune response in murine polymicrobial sepsis微分作用对cd80和cd86在先天免疫反应的调节在脓毒症小鼠幼童腹壁薄弱.pdfVIP

Differential Role for CD80 and CD86 in the Regulation of the Innate Immune Response in Murine Polymicrobial Sepsis 1 1 1 2 1 1 Anna Nolan , Hiroshi Kobayashi , Bushra Naveed , Ann Kelly , Yoshihiko Hoshino , Satomi Hoshino , 2 1 1 2 Matthew R. Karulf , William N. Rom , Michael D. Weiden , Jeffrey A. Gold * 1 Division of Pulmonary/Critical Care, New York University, School of Medicine, New York, New York, United States of America, 2 Division of Pulmonary/Critical Care, Oregon Health and Science University, Portland, Oregon, United States of America Abstract Background: Inflammation in the early stages of sepsis is governed by the innate immune response. Costimulatory molecules are a receptor/ligand class of molecules capable of regulation of inflammation in innate immunity via macrophage/neutrophil contact. We recently described that CD80/86 ligation is required for maximal macrophage activation and CD80/862/ 2 mice display reduced mortality and inflammatory cytokine production after cecal ligation and puncture (CLP). However, these data also demonstrate differential regulation of CD80 and CD86 expression in sepsis, suggesting a divergent role for these receptors. Therefore, the goal of this study was to determine the individual contribution of CD80/86 family members in regulating inflammation in sepsis. Methodology/Principal Findings: CD802/ 2 mice had improved survival after CLP when compared to WT or CD862/ 2 mice. This was associated with preferential attenuati