Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 4, Pages 2336-2342Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.4.2336
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- NEI NIH HHS [EY12370, R01 EY10559, EY11234, R01 EY010559-11, EY14102, R01 EY010559] Funding Source: Medline
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The role played by resident macropbages (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 (PNIN) 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 PNIN 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. The Journal of Immunology, 2005, 174: 2336-2342.
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