Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells

Abstract

SUMMARYAlthough 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 demonstrated by double immunostaining and flow cytometry of Langerhan's cell (LC)-enriched epidermal cell suspensions that a small subpopulation (5-6%) of epidermal resident LC (rLC) expresses receptors for C5a (C5aR). Epidermal rLC positive for C5aR show a round-shape morphology, were located next to the basement membrane, and express HLA-DR molecules higher than C5aR negative rLC. These observations suggest that rLC would express C5aR as part of their process of maturation during tissue trafficking. To investigate whether epidermal LC up-regulate C5aR along their differentiation pathway, LC were differentiated in vitro after culture in epidermal cell suspensions supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF). As a result, in vitro differentiated LC increased the expression of C5aR up to 69% of the DC population. In accordance with this observation, interdigitating DC of secondary lymphoid organs (lymph node and tonsil) also expressed C5aR. Migratory CD1a positive DC that spontaneously migrated out of dermal or split-skin organ explants were also positive for C5aR and were used for chemotaxis and chemokinesis assays in response to human recombinant C5a (rC5a). Optimum migration to rC5a was observed at 10 ÿ 8 M with a sigmoidal dose-response curve. Checkboard analysis demonstrated that locomotion in response to rC5a was chemotaxis and not chemokinesis.

Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation

“…Broadly similar results have been described for CD34 + cell-derived DC [27] as well as responses to C5a in Langerhans cells [28]. Chemokine receptors on DC are now being characterized [25,[29][30][31].…”

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

“…While C5a functions as a potent chemotactic factor for most leukocytes both in vitro and in vivo (9,(27)(28)(29), C3a is only a moderately effective chemoattractant for various leukocytes in vitro. Even cell types that showed a modest chemotactic response to C3a in vitro (i.e., eosinophils) failed to be chemoattracted by C3a in vivo (29).…”

Direct transfection and activation of human cutaneous dendritic cells

“…In the skin, different proinflammatory mediators can initiate the process of mobilization of LC. 5,7,22 Spontaneous LC migration from mouse or human skin explants has also been described. 23 Our data suggest that the delivery of either gold coated with DNA, or gold particles alone, may provide a signal for LC activation and mobilization.…”