CLONING AND DIFFERENTIAL TISSUE-SPECIFIC EXPRESSION OF 3 MOUSE BETA-CHEMOKINE RECEPTOR-LIKE GENES, INCLUDING THE GENE FOR A FUNCTIONAL MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RECEPTOR

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES, members of the beta 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-1 alpha receptor (MIP-1 alpha R) and two for orphan receptors provisionally designated MIP-1 alpha receptor-like 1 and 2 (MIP 1 alpha RL1 and 2). Their deduced sequences are 80, 62, and 63% identical to the human. MIP-1 alpha/RANTES receptor, respectively. K562 cells stably transfected with MIP-1 alpha R specifically bound I-125-human MLP-1 alpha and I-125-human RANTES with high affinity. The rank order of beta chemokine competition for I-125-human MIP-1 alpha binding was human MIP-1 alpha > mouse MLP-1 alpha similar to RANTES similar to MIP-1 beta > MCP-1. However, human RANTES was similar to 100-fold less potent as a calcium-mobilizing agonist for MIP-1 alpha R than either human or mouse MIP-1 alpha, which matched the selectivity of mouse leukocytes for calcium mobilization by MIP-1 alpha and RANTES. No other beta or a chemokines tested were agonists for MIP-1 alpha R. RNA for all three genes was detected in mouse leukocytes, but unique patterns of expression were identified in solid organs: MIP-1 alpha R, heart, spleen, and lung; MIP-1 alpha RL1, skeletal muscle; and MIP-1(alpha RL2, spleen and liver. These data identify potentially important new targets for beta chemokine action in the mouse.