Conditional macrophage ablation demonstrates that resident macrophages initiate acute peritoneal inflammation.
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.
Cailhier
Jean Francois
JF
Phagocyte Laboratory, Medical Research Council Center for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
Partolina
Marina
M
Vuthoori
Srilatha
S
Wu
Shengji
S
Ko
Kyung
K
Watson
Simon
S
Savill
John
J
Hughes
Jeremy
J
Lang
Richard A
RA
D000208:Acute Disease; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition; D019743:Chemokines, CXC / Q000096:biosynthesis; D003433:Crosses, Genetic; D004167:Diphtheria Toxin / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D006131:Growth Inhibitors / Q000378:metabolism / Q000633:toxicity; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology; D009928:Organ Specificity / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D039481:CD11b Antigen; D019743:Chemokines, CXC; D004167:Diphtheria Toxin; D006131:Growth Inhibitors; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface