Dhaliwal, Kevin and Scholefield, Emma and Ferenbach, David and Gibbons, Michael and Duffin, Rodger and Dorward, David A. and Morris, Andrew Conway and Humphries, Duncan and MacKinnon, Alison and Wilkinson, Tom S. and Wallace, William A. H. and van Rooijen, Nico and Mack, Matthias and Rossi, Adriano G. and Davidson, Donald J. and Hirani, Nik and Hughes, Jeremy and Haslett, Chris and Simpson, A. John (2012) Monocytes Control Second-Phase Neutrophil Emigration in Established Lipopolysaccharide-induced Murine Lung Injury. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 186 (6). pp. 514-524. ISSN 1073-449X,
Full text not available from this repository. (Request a copy)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 wsubpopulations 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONDITIONAL MACROPHAGE ABLATION; RESIDENT ALVEOLAR MACROPHAGES; RESPIRATORY-DISTRESS-SYNDROME; INFLAMMATORY MONOCYTES; PULMONARY INFLAMMATION; MARGINATED MONOCYTES; CHEMOKINE PRODUCTION; BLOOD MONOCYTES; DENDRITIC CELLS; MICE; acute lung injury; LPS; monocytes; neutrophils |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2020 05:37 |
| Last Modified: | 06 May 2020 05:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18107 |
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