The accumulation of dendritic cells in the lung is impaired in CD18(-/-) but not in ICAM-1(-/-) mutant mice

Bone marrow-derived dendritic cell (DC) precursors migrate via the blood st ream to peripheral tissues to adopt their sentinel function. To identify fa ctors facilitating their emigration to the lung, mutant mice deficient in E -selectin, P-selectin, E/P-selectin, ICAM-1, or CD18 and their respective c ontrols were examined. DCs and monocytes/macrophages were immunolabeled wit h 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 a nd 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 ot her, related gene products. Therefore, we examined the expression of VCAM-1 . Increased numbers of arteries exhibited continuous luminal VCAM-1 stainin g in both CD18(-/-) and ICAM-1(-/-) mutants, VCAM-1 expression was absent i n pulmonary capillaries and unchanged in veins. These data suggest that und er nonperturbing conditions, CD18-mediated adhesion is required for the ful l complement of DC precursors to accumulate in the lungs, However, the defe ct in CD18(-/-) mice is partial, suggesting that CD18-independent adhesion occurs. The alternative pathway may involve VLA-4/VCAM-1 in arteries and ve nules but not in capillaries. The smaller defect in ICAM-1(-/-) mice sugges ts that the CD11/CD18 complex recognizes ligands other than ICAM-1 at some sites.