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

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...

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Published in:	American journal of respiratory and critical care medicine 2012-09, Vol.186 (6), p.514-524
Main Authors:	DHALIWAL, Kevin, SCHOLEFIELD, Emma, WALLACE, William A. H, ROOIJEN, Nico Van, MACK, Matthias, ROSSI, Adriano G, DAVIDSON, Donald J, HIRANI, Nik, HUGHES, Jeremy, HASLETT, Chris, JOHN SIMPSON, A, FERENBACH, David, GIBBONS, Michael, DUFFIN, Rodger, DORWARD, David A, CONWAY MORRIS, Andrew, HUMPHRIES, Duncan, MACKINNON, Alison, WILKINSON, Tom S
Format:	Article
Language:	eng
Subjects:	Ablation Acute Lung Injury - pathology Acute Lung Injury - physiopathology Analysis of Variance Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antibodies Biological and medical sciences Bronchoalveolar Lavage Fluid - cytology Cell Movement - immunology Cell Movement - physiology Chemokines Clodronic Acid - pharmacology Cloning Diphtheria Disease Models, Animal Emigration Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Immunohistochemistry Inflammation Injuries of the thorax. Foreign bodies. Diseases due to physical agents Intensive care medicine Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - immunology Lipopolysaccharides - pharmacology Macrophages - cytology Macrophages - immunology Male Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Monocytes - cytology Monocytes - immunology Mortality Neutrophils Neutrophils - cytology Neutrophils - physiology Random Allocation Recruitment Statistics, Nonparametric Traumas. Diseases due to physical agents
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Summary:	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. To determine the influence of peripheral blood monocytes (PBMs) in established ALI. 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. 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. These results suggest that PBMs, or the mechanisms by which they influence pulmonary neutrophil emigration, could represent therapeutic targets in established ALI.
ISSN:	1073-449X 1535-4970