Blood monocyte migration to acute lung inflammation involves both CD11/CD18 and very late activation antigen-4-dependent and independent pathways.
In acute lung inflammation, blood neutrophils and monocytes migrate into the lung parenchyma and bronchoalveolar space. The infiltration of the inflamed lung by monocytes is poorly understood because of difficulties in quantifying these cells in the presence of resident macrophages. Radiolabeled monocytes were used to study monocyte migration into the inflamed rat lung. Monocytes and neutrophils were purified from blood, labeled with 51Cr and (111)In, respectively, and injected i.v. into rats given an intratracheal injection of LPS. The accumulation of 51Cr-labeled monocytes increased > 10-fold in the lung parenchyma and 170-fold in the bronchoalveolar lavage (BAL) 18 h after LPS. (111)In-labeled neutrophils increased > 30-fold in the lung tissue and 500-fold in the BAL. Treatment of rats with a blocking anti-CD18 mAb inhibited monocyte accumulation in the lung and BAL by about 30%, whereas blocking very late activation Ag-4 (VLA-4) had no effect. Combined blockade of VLA-4 and CD18 inhibited approximately 30% of the migration to the lung parenchyma, but decreased the BAL by 80%. Monocyte migration to cutaneous inflammation was completely abolished by the combined mAb treatment. Neutrophil accumulation in the lung and BAL was not decreased by blocking either CD18 or VLA-4 and was only partially reduced by blocking CD18 plus VLA-4. Thus, monocyte migration to the LPS inflamed lung is substantially CD11/CD18 and VLA-4 independent, but accumulation in BAL is mediated by CD18 and VLA-4. Monocytes as well as neutrophils may use a previously unrecognized endothelial adhesion and migration pathway in the lung.
Li
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Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Miyasaka
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Issekutz
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D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018845:CD11 Antigens / Q000502:physiology*; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology*; D007249:Inflammation / Q000097:blood / Q000276:immunology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D008070:Lipopolysaccharides; D016201:Receptors, Lymphocyte Homing