The role played by resident macrophages (Mφ) in the initiation of peritoneal inflammation is currently unclear. We have used a conditional Mφ ablation strategy to determine the role of resident peritoneal Mφ in the regulation of neutrophil (PMN) recruitment in experimental peritonitis. We developed a novel conditional Mφ 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 Mφ populations in the peritoneum as well as the kidney, and ovary. In experimental peritonitis, resident Mφ ablation resulted in a dramatic attenuation of PMN infiltration that was rescued by the adoptive transfer of resident nontransgenic Mφ. Attenuation of PMN infiltration was associated with diminished CXC chemokine production at 1 h. These studies indicate a key role for resident peritoneal Mφ in sensing perturbation to the peritoneal microenvironment and regulating PMN infiltration.

Lymphoplasmacytic sclerosing pancreatitis ("autoimmune" pancreatitis) is the best-known manifestation of an unusual corticosteroid-sensitive systemic fibrosclerotic disease that is associated with high plasma immunoglobulin G4 (IgG4) and tissue infiltration with IgG4-secreting plasma cells. Pancreatic and biliary manifestations of this condition are well-reported, but reports of other systemic involvement are few. We report here a case of initially unrecognized autoimmune pancreatitis followed 5 years later by a focal sclerosing lymphoplasmacytic tubulointerstitial nephritis and concurrent membranous nephropathy. The patient presented with hypertension, a raised serum creatinine, proteinuria, elevated serum IgG4, and eosinophilia. Immunolabeling of renal tissue showed numerous IgG4 positive plasma cells with peritubular and glomerular subepithelial IgG4 deposition. On steroid therapy serum IgG4 levels normalized, the eosinophilia resolved, and there was improvement in symptomatic wheeze, dry eyes, serum creatinine, and liver function tests. This case highlights a distinctive and potentially treatable form of interstitial nephritis manifesting from a systemic immune disorder, and provides circumstantial evidence to support the notion that dysregulated IgG4 can precipitate the development of a form of membranous nephropathy.

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