RECEPTOR EXPRESSION AND RESPONSIVENESS OF HUMAN DENDRITIC CELLS TO A DEFINED SET OF CC AND CXC CHEMOKINES

Dendritic cells (DC) are migratory cells that exhibit complex traffick ing properties in vivo. The present study was designed to characterize receptor expression and responsiveness to chemoattractants of human D C obtained from PBMC by culture with granulocyte/macrophage-CSF and IL -13. DC expressed appreciable levels of the CCR1, CCR2, and CCR3 recep tors for the CC chemokines and the chemokine receptors CXCR1, CXCR2, a nd CXCR4. DC increased intracellular free calcium and migrated in resp onse to the CC chemokines MCP-3, MCP-4, RANTES, MIP-1 alpha, MIP-1 bet a, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the CC che mokines MCP-1 and eotaxin had little or no activity in the concentrati on range tested (up to 1 mu g/ml). IL-8 and Gro-beta (CXC) and lymphot actin (C chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet-activating factor was an active agonist. Selected ch emokines active on DC in terms of migration and calcium fluxes were ex amined for their capacity to modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was active, MCP-1, MCP-3, MIP-1 a lpha, and RANTES did not affect these two responses. Thus, among hemop oietic elements, DC respond to a unique set of CC and CXC chemokines, and their responsiveness is restricted to migration with no effect on Ag capture and presentation. Chemokines may play a role in the traffic king of DC under resting or stimulated conditions. Chemokine receptors expressed in DC are likely to underlie HIV infection of this cell typ e.