Resident pleural macrophages are key orchestrators of neutrophil recruitment in pleural inflammation.
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.
Cailhier
Jean François
JF
Phagocyte Laboratory, MRC Center for Inflammation Research, University of Edinburgh, Teviot Place, Edinburgh, UK, EH8 9AG.
Sawatzky
Deborah A
DA
Kipari
Tiina
T
Houlberg
Kris
K
Walbaum
Dave
D
Watson
Simon
S
Lang
Richard A
RA
Clay
Spike
S
Kluth
David
D
Savill
John
J
Hughes
Jeremy
J
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*
D004167:Diphtheria Toxin; D002351:Carrageenan