PROFILE OF HUMAN MACROPHAGE TRANSCRIPTS - INSIGHTS INTO MACROPHAGE BIOLOGY AND IDENTIFICATION OF NOVEL CHEMOKINES

High throughput partial sequencing of randomly selected cDNA clones ha s proven to be a powerful tool for examining the relative abundance of mRNAs and for the identification of novel gene products. Because of t he important role played by macrophages in immune and inflammatory res ponses, we sequenced over 3000 randomly selected cDNA clones from a hu man macrophage library. These sequences represent a molecular inventor y of mRNAs from macro phages and provide a catalog of highly expressed transcripts. Two of the most abundant clones encode recently identifi ed CC chemokines. Macrophage-derived chemokine (MDC) plays a complex r ole in immunoregulation and is a potent chemoattractant for dendritic cells, T cells, and natural killer cells. The chemokine receptor CCR4 binds MDC with high affinity and also responds by calcium flux and che motaxis. CCR4 has been shown to be expressed by Th2 type T cells. Rece nt studies also implicate MDC as a major component of the host defense against human immunodeficiency virus.