Cailhier Jean Francois, Partolina Marina, Vuthoori Srilatha, Wu Shengji, Ko Kyung, Watson Simon, Savill John, Hughes Jeremy, Lang Richard A
Phagocyte Laboratory, Medical Research Council Center for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
J Immunol. 2005 Feb 15;174(4):2336-42. doi: 10.4049/jimmunol.174.4.2336.
The role played by resident macrophages (Mphi) in the initiation of peritoneal inflammation is currently unclear. We have used a conditional Mphi ablation strategy to determine the role of resident peritoneal Mphi in the regulation of neutrophil (PMN) recruitment in experimental peritonitis. We developed a novel conditional Mphi ablation transgenic mouse (designated CD11bDTR) based upon CD11b promoter-mediated expression of the human diphtheria toxin (DT) receptor. The murine DT receptor binds DT poorly such that expression of the human receptor confers toxin sensitivity. Intraperitoneal injection of minute (nanogram) doses of DT results in rapid and marked ablation of F4/80-positive Mphi populations in the peritoneum as well as the kidney, and ovary. In experimental peritonitis, resident Mphi ablation resulted in a dramatic attenuation of PMN infiltration that was rescued by the adoptive transfer of resident nontransgenic Mphi. Attenuation of PMN infiltration was associated with diminished CXC chemokine production at 1 h. These studies indicate a key role for resident peritoneal Mphi in sensing perturbation to the peritoneal microenvironment and regulating PMN infiltration.
目前尚不清楚驻留巨噬细胞（Mphi）在腹膜炎症起始过程中所起的作用。我们采用了一种条件性Mphi消融策略，以确定驻留腹膜Mphi在实验性腹膜炎中对中性粒细胞（PMN）募集的调节作用。我们基于CD11b启动子介导的人白喉毒素（DT）受体表达，开发了一种新型的条件性Mphi消融转基因小鼠（命名为CD11bDTR）。小鼠DT受体与DT的结合能力较差，因此人受体的表达赋予了毒素敏感性。腹腔注射微量（纳克）剂量的DT会导致腹膜以及肾脏和卵巢中F4/80阳性Mphi群体迅速且显著地消融。在实验性腹膜炎中，驻留Mphi消融导致PMN浸润显著减弱，而通过移植驻留非转基因Mphi可使其恢复。PMN浸润的减弱与1小时时CXC趋化因子产生减少有关。这些研究表明，驻留腹膜Mphi在感知腹膜微环境的扰动以及调节PMN浸润方面起着关键作用。
