title: The accumulation of dendritic cells in the lung is impaired in CD18-/- but not in ICAM-1-/- mutant mice.
abstract: Bone marrow-derived dendritic cell (DC) precursors migrate via the blood stream to peripheral tissues to adopt their sentinel function. To identify factors facilitating their emigration to the lung, mutant mice deficient in E-selectin, P-selectin, E/P-selectin, ICAM-1, or CD18 and their respective controls were examined. DCs and monocytes/macrophages were immunolabeled with M5/114 and MOMA-2 mAbs, respectively, and quantified morphometrically. Of these genotypes, the numbers of DC and MOMA-2+ cells were significantly less only in the lungs of CD18-/- mice by 68 and 35% in alveolar walls and by 28 and 26% in venous walls, respectively. DCs were reduced by 30 and 41% around large and small airways, respectively, but the number of MOMA-2+ cells in these locations was not significantly different from controls. Ablation of a single gene may be associated with augmented expression of other, related gene products. Therefore, we examined the expression of VCAM-1. Increased numbers of arteries exhibited continuous luminal VCAM-1 staining in both CD18-/- and ICAM-1-/- mutants. VCAM-1 expression was absent in pulmonary capillaries and unchanged in veins. These data suggest that under nonperturbing conditions, CD18-mediated adhesion is required for the full complement of DC precursors to accumulate in the lungs. However, the defect in CD18-/- mice is partial, suggesting that CD18-independent adhesion occurs. The alternative pathway may involve VLA-4/VCAM-1 in arteries and venules but not in capillaries. The smaller defect in ICAM-1-/- mice suggests that the CD11/CD18 complex recognizes ligands other than ICAM-1 at some sites.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, and Physiology Program, Harvard School of Public Health, Boston, MA 02129, USA. schneebe@helix.mgh.harvard.edu
authors.forename: E E
authors.initials: EE
authors.lastname: Schneeberger
authors.forename: Q
authors.initials: Q
authors.lastname: Vu
authors.forename: B W
authors.initials: BW
authors.lastname: LeBlanc
authors.forename: C M
authors.initials: CM
authors.lastname: Doerschuk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D018821:CD18 Antigens / Q000235:genetics*; D002196:Capillaries / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007958:Leukocyte Count; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology; D007970:Leukopenia / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000276:immunology; D011651:Pulmonary Artery / Q000276:immunology / Q000378:metabolism; D011667:Pulmonary Veins / Q000276:immunology / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1