title: Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness.
abstract: BACKGROUND
  Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin.
  
  
  METHODS
  Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS.
  
  
  RESULTS
  We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF) cytokine and chemokine levels (TNFalpha, MIP-2, CCL2) and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin.
  
  
  CONCLUSIONS
  These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine and Infectious Diseases, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany. mirko.steinmueller@innere.med.uni-giessen.de
authors.forename: Mirko
authors.initials: M
authors.lastname: Steinmüller
authors.forename: Mrigank
authors.initials: M
authors.lastname: Srivastava
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: John W
authors.initials: JW
authors.lastname: Christman
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lohmeyer
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000276:immunology*
chemical_list: C515335:Ccr2 protein, mouse; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D019707:Receptors, Chemokine