Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells

Dendritic cells (DC) are highly specialized APC that are critical for the i nitiation of T cell-dependent immune responses. DC exert a sentinel functio n while immature and, after activation by inflammatory stimuli or infectiou s agents, mature and migrate into lymphoid organs to prime T cells. We have analyzed integrin expression on monocyte-derived DC (MDDC) and found that expression of CD49d integrins (CD49d/CD29 and CD49d/beta 7) was induced/up- regulated during TNF-alpha- or LPS-initiated MDDC maturation, reflecting th e induction/up-regulation of CD49d and beta 7 mRNA, CD49d mRNA steady-state level increased more than 10 times during maturation, with the highest lev els observed 24 h after TNF-alpha treatment. CD49d integrin expression conf erred mature MDDC,vith an elevated capacity to adhere to the CS-1 fragment of fibronectin, and also mediated transendothelial migration of mature MDDC , Up-regulation of CD49d integrin expression closely paralleled that of the mature DC marker CD83. CD49d integrin expression was dependent on cell mat uration, as its induction was abrogated by N-acetylcysteine, which inhibits NF-kappa B activation and the functional and phenotypic maturation of MDDC . Moreover, CD49d integrin up-regulation and MDDC maturation were prevented by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase, but were almost unaffected by the mitogen-activated protein/extracellular signal-related kinase kinase 1/2 inhibitor PD98059, Our results support the existence of a link between functional and phenotypic maturation of MDDC a nd CD49d integrin expression, thus establishing CD49d as a maturation marke r for MDDC. The differential expression of CD49d on immature and mature MDD C might contribute to their distinct motility capabilities and mediate matu re DC migration into lymphoid organs.