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Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells
A Puig-Kröger1, F Sanz-Rodríguez, N Longo
1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain. Servicio de Inmuno-Oncología, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Journal of Immunology (Baltimore, Md. : 1950)
|October 18, 2000
Summary
Dendritic cell (DC) maturation up-regulates CD49d integrin expression, enhancing their ability to migrate. This finding establishes CD49d as a key marker for mature dendritic cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial antigen-presenting cells (APCs) initiating T cell responses.
- Immature DCs act as sentinels, maturing upon activation to prime T cells in lymphoid organs.
Purpose of the Study:
- To investigate integrin expression, specifically CD49d, during monocyte-derived DC (MDDC) maturation.
- To determine the role of CD49d in MDDC function and its potential as a maturation marker.
Main Methods:
- Analysis of integrin expression (CD49d/CD29, CD49d/beta7) on MDDC during maturation induced by TNF-alpha or LPS.
- Quantification of CD49d and beta7 mRNA levels.
- Assessment of MDDC adhesion to fibronectin and transendothelial migration.
- Inhibition studies using N:-acetylcysteine (NF-kappaB inhibitor) and SB203580 (p38 MAPK inhibitor).
Main Results:
- CD49d integrin expression and mRNA levels were significantly induced during MDDC maturation.
- Mature MDDC expressing CD49d showed increased adhesion to fibronectin and enhanced transendothelial migration.
- CD49d up-regulation correlated with the mature DC marker CD83 and was dependent on NF-kappaB and p38 MAPK pathways.
- Inhibition of p38 MAPK prevented CD49d up-regulation and MDDC maturation.
Conclusions:
- CD49d integrin expression is a reliable marker of MDDC functional and phenotypic maturation.
- Differential CD49d expression on immature versus mature MDDC influences their migratory properties.
- CD49d plays a role in mediating the migration of mature DCs into lymphoid organs.