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Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice.

Maus UA, Koay MA, Delbeck T, Mack M, Ermert M, Ermert L, Blackwell TS, Christman JW, Schlöndorff D, Seeger W, Lohmeyer J
Am J Physiol Lung Cell Mol Physiol. 2002 282 (6): L1245-52

PMID: 12003780 · DOI:10.1152/ajplung.00453.2001

Intratracheal instillation of the monocyte chemoattractant JE/monocyte chemoattractant protein (MCP)-1 in mice was recently shown to cause increased alveolar monocyte accumulation in the absence of lung inflammation, whereas combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute lung inflammation with early alveolar neutrophil and delayed alveolar monocyte influx. We evaluated the role of resident alveolar macrophages (rAM) in these leukocyte recruitment events and related phenomena of lung inflammation. Depletion of rAM by pretreatment of mice with liposomal clodronate did not affect the JE/MCP-1-driven alveolar monocyte accumulation, despite the observation that rAM constitutively expressed the JE/MCP-1 receptor CCR2, as analyzed by flow cytometry and immunohistochemistry. In contrast, depletion of rAM largely suppressed alveolar cytokine release as well as neutrophil and monocyte recruitment profiles upon combined JE/MCP-1/LPS treatment. Despite this strongly attenuated alveolar inflammatory response, increased lung permeability was still observed in rAM-depleted mice undergoing JE/MCP-1/LPS challenge. Lung leakage was abrogated by codepletion of circulating neutrophils or administration of anti-CD18. Collectively, rAM are not involved in JE/MCP-1-driven alveolar monocyte recruitment in noninflamed lungs but largely contribute to the alveolar cytokine response and enhanced early neutrophil and delayed monocyte influx under inflammatory conditions (JE/MCP-1/LPS deposition). Loss of lung barrier function observed under these conditions is rAM independent but involves circulating neutrophils via beta(2)-integrin engagement.

MeSH Terms (23)

Animals Antibodies, Monoclonal Bronchoalveolar Lavage Fluid CD18 Antigens Cell Count Chemokine CCL2 Chemotaxis, Leukocyte Cytokines Escherichia coli Female Flow Cytometry Immunohistochemistry Instillation, Drug Lipopolysaccharides Macrophages, Alveolar Mice Mice, Inbred BALB C Monocytes Pneumonia Pulmonary Alveoli Receptors, CCR2 Receptors, Chemokine Trachea

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