Cloning and differential tissue-specific expression of three mouse β chemokine receptor-like genes, including the gene for a functional macrophage inflammatory protein-1α receptor

Abstract

Macrophage inflammatory protein-1α (MIP-1α) and RANTES, members of the β chemokine family of leukocyte chemoattractants, bind to a common seven-transmembrane-domain human receptor. We have now cloned three related mouse genes: one for a selective MIP-1α receptor (MIP-1αR) and two for orphan receptors provisionally designated MIP-1α receptor-like 1 and 2 (MIP-1αRL1 and 2). Their deduced sequences are 80, 62, and 63% identical to the human MIP-1α/RANTES receptor, respectively. K562 cells stably transfected with MIP-1αR specifically bound 125I-human MIP-1α and 125I-human RANTES with high affinity. The rank order of β chemokine competition for 125I-human MIP-1α binding was human MIP-1α > mouse MIP-1α ∼ RANTES ∼ MIP-1β > MCP-1. However, human RANTES was ∼100-fold less potent as a calcium-mobilizing agonist for MIP-1αR than either human or mouse MIP-1α, which matched the selectivity of mouse leukocytes for calcium mobilization by MIP-1α and RANTES. No other β or α chemokines tested were agonists for MIP-1αR. RNA for all three genes was detected in mouse leukocytes, but unique patterns of expression were identified in solid organs: MIP-1αR, heart, spleen, and lung; MIP-1αRL1, skeletal muscle; and MIP-1αRL2, spleen and liver. These data identify potentially important new targets for β chemokine action in the mouse.