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A cDNA encoding a novel human chemokine was isolated by random sequencing of human monocyte-derived macrophage cDNA clones. This protein is called macrophage-derived chemokine (MDC) because it appears to be synthesized exclusively by cells of the macrophage lineage. MDC has a 4-cysteine motif and other highly conserved residues characteristic of CC chemokines, yet it shares 35% homology with any known chemokine. MDCs are a unique member of the CC chemokine family and may play fundamental roles in the function of dendritic cells, natural killer cells and monocytes.