EXPRESSION AND MODULATION OF C5A RECEPTOR (CD88) ON SKIN DENDRITIC CELLS - CHEMOTACTIC EFFECT OF C5A ON SKIN MIGRATORY DENDRITIC CELLS

Although it is known that dendritic cells (DC) migrate in response to inflammatory stimuli, there is little information about the expression of receptors for chemotactic factors on DC. The present study has dem onstrated by double immunostaining and flow cytometry of Langerhan's c ell (LC)enriched epidermal cell suspensions that a small subpopulation (5-6%) of epidermal resident LC (rLC) expresses receptors for C5a (C5 aR). Epidermal rLC positive For C5aR show a round-shape morphology, we re located next to the basement membrane, and express HLA-DR molecules higher than C5aR negative rLC. These observations suggest that rLC wo uld express C5aR as part of their process of maturation during tissue trafficking. To investigate whether epidermal LC upregulate C5aR along their differentiation pathway, LC were differentiated in vitro after culture in epidermal cell suspensions supplemented with granulocyte-ma crophage colony-stimulating factor (GM-CSF). As a result, in vitro dif ferentiated LC increased the expression of C5aR up to 69% of the DC po pulation. In accordance with this observation, interdigitating DC of s econdary lymphoid organs (lymph node and tonsil) also expressed C5aR. Migratory CD1a positive DC that spontaneously migrated out of dermal o r split-skin organ explants were also positive for C5aR and were used for chemotaxis and chemokinesis assays in response to human recombinan t C5a (rC5a). Optimum migration to rC5a was observed at 10(-8) M With a sigmoidal dose-response curve. Checkboard analysis demonstrated that locomotion in response to rC5a was chemotaxis and not chemokinesis.