INFLUENCE OF EXTRACELLULAR-MATRIX PROTEINS ON THE DEVELOPMENT OF CULTURED HUMAN DENDRITIC CELLS

The development of dendritic cells (DC) is still only partly understoo d. Recently established culture systems using CD34(+) cells or monocyt es as precursor cells for the generation of DC indicate the necessity of pro-inflammatory cytokines for their development. In vivo the conta ct to other cells or to the proteins of the extracellular matrix might also be essential for their development. In our experiments we used g ranulocyte-macrophage colony-stimulating factor-and IL-4-treated human monocytes as precursor cells to investigate the interaction of DC at different maturation stages with the matrix proteins fibronectin, coll agen type I and collagen type IV. We demonstrate a strong beta(1)-inte grin-mediated adherence of immature DC to fibronectin that is lost com pletely during maturation. The binding to collagen type I was less str ong but induced a maturation of the precursor cells. After 3 days of c ulture on this protein, the cells showed all features of fully matured DC such as expression of CD83 and an excellent allostimulatory capaci ty. The reason for this effect was shown to be the induction of TNF-al pha production by the DC themselves. In contrast to the adhesion to fi bronectin, the maturation and the cytokine production of DC induced by collagen type I could not be inhibited by blocking of beta(1)-integri ns. These results indicate that proteins of the extracellular matrix p lay an important role in the development and function of human DC.