title: Resident pleural macrophages are key orchestrators of neutrophil recruitment in pleural inflammation.
abstract: BACKGROUND
  The role played by resident pleural macrophages in the initiation of pleural inflammation is currently unclear.
  
  
  OBJECTIVE
  To evaluate the role of resident pleural macrophages in the initiation of inflammation.
  
  
  METHODS
  We have used a conditional macrophage ablation strategy to determine the role of resident pleural macrophages in the regulation of neutrophil recruitment in a murine model of experimental pleurisy induced by the administration of carrageenan and formalin- fixed Staphylococcus aureus.
  
  
  RESULTS
  Conditional macrophage ablation mice express the human diphtheria toxin receptor under the control of the CD11b promoter such that the administration of diphtheria toxin induces ablation of nearly 97% of resident macrophages. Ablation of resident pleural macrophages before the administration of carrageenan or S. aureus dramatically reduced neutrophil influx into the pleural cavity. In the carrageenan model, the reduction in neutrophil infiltration was associated with marked early reduction in the level of macrophage inflammatory protein 2 as well as reduced levels of various cytokines, including tumor necrosis factor alpha, interleukin 6, and interleukin 10. Adoptive transfer of nontransgenic macrophages partially restored neutrophil infiltration. We also stimulated macrophage-depleted and nondepleted pleural cell populations with carrageenan in vitro and determined the production of chemokines and cytokines. Chemokine and cytokine production was markedly reduced by macrophage depletion, reinforcing the role of resident pleural macrophages in the generation of mediators that initiate acute inflammation.
  
  
  CONCLUSIONS
  These studies indicate a critical role for resident pleural macrophages in sensing perturbation to the local microenvironment and orchestrating subsequent neutrophil infiltration.
authors.affiliation: Phagocyte Laboratory, MRC Center for Inflammation Research, University of Edinburgh, Teviot Place, Edinburgh, UK, EH8 9AG.
authors.forename: Jean François
authors.initials: JF
authors.lastname: Cailhier
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Sawatzky
authors.forename: Tiina
authors.initials: T
authors.lastname: Kipari
authors.forename: Kris
authors.initials: K
authors.lastname: Houlberg
authors.forename: Dave
authors.initials: D
authors.lastname: Walbaum
authors.forename: Simon
authors.initials: S
authors.lastname: Watson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.forename: Spike
authors.initials: S
authors.lastname: Clay
authors.forename: David
authors.initials: D
authors.lastname: Kluth
authors.forename: John
authors.initials: J
authors.lastname: Savill
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hughes
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D004167:Diphtheria Toxin / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D010994:Pleura / Q000166:cytology* / Q000276:immunology*; D010998:Pleurisy / Q000276:immunology*
chemical_list: D004167:Diphtheria Toxin; D002351:Carrageenan