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.

The α1β1 and αEβ7 Integrins Define a Subset of Dendritic Cells in Peripheral Lymph Nodes with Unique Adhesive and Antigen Uptake Properties

“…Similar studies have also demonstrated a role for ␣ 6 integrins, which mediate adhesion to the ECM protein laminin, in Langerhans cell migration out of the skin (19). In addition to the role of integrins in DC homing to the LN, ␤ 2 integrins are critical for the homeostatic accumulation of DC within the lungs (20).…”

Functional Consequences of Integrin Gene Mutations in Mice

“…47 ␤ 2 integrin also plays an important role in T cell proliferation 44 and contributes to the accumulation of dendritic cells in the lung. 48 LFA-1 and, to a lesser degree, Mac-1 contribute to neutrophil adhesion to endothelium. In a tumor necrosis factor (TNF)-induced air pouch inflammation model, neutrophil migration was equally reduced in ␤ 2 -deficient and LFA-1-deficient mice, whereas mice lacking Mac-1 showed a marked increase of neutrophil extravasation.…”

Migration of immature mouse DC across resting endothelium is mediated by ICAM‐2 but independent of β2‐integrins and murine DC‐SIGN homologues

“…Schneeberger et al [41] found a partial reduction in the number of DC in the lungs of CD18-deficient mice, although it is not clear whether this is due to a defect in TEM itself or to spontaneous inflammation observed in such mice [32], which might lead to subsequent depletion of DC from inflamed organs. In contrast to the data from the lung model, Grabbe et al [42] observed no differences in the migration of CD18-deficient immature DC to the inflamed skin in a model of acute contact dermatitis.…”