title: Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury.
abstract: BACKGROUND
  Acute lung injury (ALI) is an important cause of morbidity and mortality, with no currently effective pharmacological therapies. Neutrophils have been specifically implicated in the pathogenesis of ALI, and there has been significant research into the mechanisms of early neutrophil recruitment, but those controlling the later phases of neutrophil emigration that characterize disease are poorly understood.
  
  
  OBJECTIVE
  To determine the influence of peripheral blood monocytes (PBMs) in established ALI.
  
  
  METHODS
  In a murine model of LPS-induced ALI, three separate models of conditional monocyte ablation were used: systemic liposomal clodronate (sLC), inducible depletion using CD11b diphtheria toxin receptor (CD11b DTR) transgenic mice, and antibody-dependent ablation of CCR2(hi) monocytes.
  
  
  RESULTS
  PBMs play a critical role in regulating neutrophil emigration in established murine LPS-induced lung injury. Gr1(hi) and Gr1(lo) PBM subpopulations contribute to this process. PBM depletion is associated with a significant reduction in measures of lung injury. The specificity of PBM depletion was demonstrated by replenishment studies in which the effects were reversed by systemic PBM infusion but not by systemic or local pulmonary infusion of mature macrophages or lymphocytes.
  
  
  CONCLUSIONS
  These results suggest that PBMs, or the mechanisms by which they influence pulmonary neutrophil emigration, could represent therapeutic targets in established ALI.
authors: MRC Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK. kdhaliwa@staffmail.ed.ac.uk
authors: Kevin
authors: K
authors: Dhaliwal
authors: Emma
authors: E
authors: Scholefield
authors: David
authors: D
authors: Ferenbach
authors: Michael
authors: M
authors: Gibbons
authors: Rodger
authors: R
authors: Duffin
authors: David A
authors: DA
authors: Dorward
authors: Andrew Conway
authors: AC
authors: Morris
authors: Duncan
authors: D
authors: Humphries
authors: Alison
authors: A
authors: MacKinnon
authors: Tom S
authors: TS
authors: Wilkinson
authors: William A H
authors: WA
authors: Wallace
authors: Nico
authors: N
authors: van Rooijen
authors: Matthias
authors: M
authors: Mack
authors: Adriano G
authors: AG
authors: Rossi
authors: Donald J
authors: DJ
authors: Davidson
authors: Nik
authors: N
authors: Hirani
authors: Jeremy
authors: J
authors: Hughes
authors: Chris
authors: C
authors: Haslett
authors: A John
authors: AJ
authors: Simpson
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000276:immunology* / Q000502:physiology; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D011897:Random Allocation; D018709:Statistics, Nonparametric
chemical_list: D008070:Lipopolysaccharides; D004002:Clodronic Acid