Projects per year
Abstract
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 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. Objectives: 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. Measurements and Main 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.
Original language | English |
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Pages (from-to) | 514-524 |
Number of pages | 11 |
Journal | American Journal of Respiratory and Critical Care Medicine |
Volume | 186 |
Issue number | 6 |
DOIs | |
Publication status | Published - 15 Sept 2012 |
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Dive into the research topics of 'Monocytes Control Second-Phase Neutrophil Emigration in Established Lipopolysaccharide-induced Murine Lung Injury'. Together they form a unique fingerprint.Projects
- 3 Finished
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PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY
Iredale, J. (Principal Investigator)
1/09/12 → 31/08/16
Project: Research
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Monocyte-based gene therapy for acute neutrophil-medicated tissue injury
Dhaliwal, K. (Principal Investigator) & Simpson, J. (Co-investigator)
1/02/08 → 31/01/10
Project: Research
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Induction of neutrophil apoptosis and treatment of severe lung inflammation
Rossi, A. (Principal Investigator)
1/09/07 → 29/02/12
Project: Research