Monocytes Control Second-Phase Neutrophil Emigration in Established Lipopolysaccharide-induced Murine Lung Injury

• DOI: 10.1164/rccm.201112-2132oc
• Publication Date: 2012-07-21T10:35:52Z
• Authors: Kevin Dhaliwal; Emma Scholefield; David Ferenbach; Michael Gibbons; Rodger Duffin; David A. Dorward; Andrew Conway Morris; Duncan Humphries; Alison MacKinnon; Tom S. Wilkinson; William A. H. Wal...; Nico van Rooijen; Matthias Mack; Adriano G. Rossi; Donald J. Davidson; Nik Hirani; Jeremy Hughes; Chris Haslett; A. John Simpson
• Keywords: Neutrophil Extracellular Traps; Neutrophilia; Pathogenesis

Rationale: 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 ALI, there has significant research into mechanisms early neutrophil recruitment, but those controlling later phases emigration that characterize disease are poorly understood.Objectives: To determine influence peripheral blood monocytes (PBMs) established ALI.Methods: In a murine model LPS-induced three separate models conditional monocyte ablation were used: systemic liposomal clodronate (sLC), inducible depletion using CD11b diphtheria toxin receptor (CD11b DTR) transgenic mice, antibody-dependent CCR2hi monocytes.Measurements Main Results: PBMs play critical role regulating injury. Gr1hi Gr1lo PBM subpopulations contribute to this process. associated reduction measures The specificity was demonstrated by replenishment studies which effects reversed infusion not or local pulmonary mature macrophages lymphocytes.Conclusions: These results suggest PBMs, they emigration, could represent therapeutic targets ALI.