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 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/beta7) was induced/up-regulated during TNF-alpha- or LPS-initiated MDDC maturation, reflecting the induction/up-regulation of CD49d and beta7 mRNA. CD49d mRNA steady-state level increased more than 10 times during maturation, with the highest levels observed 24 h after TNF-alpha 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-kappaB 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.
Puig-Kröger
A
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain. Servicio de Inmuno-Oncología, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Sanz-Rodríguez
F
F
Longo
N
N
Sánchez-Mateos
P
P
Botella
L
L
Teixidó
J
J
Bernabéu
C
C
Corbí
A L
AL
D000111:Acetylcysteine / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D039441:Integrin alpha4; D039641:Integrin beta Chains; D016023:Integrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D015703:Antigens, CD; D006131:Growth Inhibitors; D039641:Integrin beta Chains; D016023:Integrins; C091368:integrin beta7; D039441:Integrin alpha4; D000111:Acetylcysteine