Human recombinant macrophage inflammatory protein-1α and -β and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes

The human macrophage inflammatory proteins-1α and -β (MIP-1α and -β), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1α and -β labeled with ¹²⁵I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1α on human monocytes and on THP-1 cells, with K(d) values of 383 pM and 450 pM, respectively. Human MIP-1α and -β had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1α and -β binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1α and -β partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1α and -β were chemotactic for human monocytes. Preincubation of monocytes with human rMIP-1α or -β markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1α or -β. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP-1α and -β, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides.