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*
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain; and
Servicio de Inmuno-Oncología, Hospital Universitario Gregorio Marañón, Madrid, Spain
Dendritic cells (DC) are highly specialized APC that are critical
for the initiation of T cell-dependent immune responses. DC exert a
sentinel function while immature and, after activation by inflammatory
stimuli or infectious 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/ß7) was induced/up-regulated during TNF-
- or
LPS-initiated MDDC maturation, reflecting the induction/up-regulation
of CD49d and ß7 mRNA. CD49d mRNA steady-state level increased more
than 10 times during maturation, with the highest levels observed
24 h after TNF- treatment. CD49d integrin expression conferred
mature MDDC with 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 maturation, as its induction was abrogated by
N-acetylcysteine, which inhibits NF-
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 and CD49d integrin expression, thus establishing CD49d as a
maturation marker for MDDC. The differential expression of CD49d on
immature and mature MDDC might contribute to their distinct motility
capabilities and mediate mature DC migration into lymphoid
organs.
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