Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice.
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.
Maus
Ulrich A
UA
Department of Internal Medicine, Division of Pneumology, Justus Liebig University, 35392 Giessen, Germany. Ulrich.A.Maus@med.uni-giessen.de
Koay
M Audrey
MA
Delbeck
Tim
T
Mack
Matthias
M
Ermert
Monika
M
Ermert
Leander
L
Blackwell
Timothy S
TS
Christman
John W
JW
Schlöndorff
Detlef
D
Seeger
Werner
W
Lohmeyer
Jürgen
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018821:CD18 Antigens / Q000187:drug effects; D002452:Cell Count; D018932:Chemokine CCL2 / Q000008:administration & dosage; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007322:Instillation, Drug; D008070:Lipopolysaccharides / Q000008:administration & dosage; D016676:Macrophages, Alveolar / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D019707:Receptors, Chemokine