THE ACTIVE MONOMERIC FORM OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA INTERACTS WITH HIGH-AFFINITY AND LOW-AFFINITY CLASSES OF RECEPTORS ON HUMAN HEMATOPOIETIC-CELLS

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and its human ho mologue GOS19.1/LD78 are members of the C-C chemokine/intercrine famil y of secreted proteins. They have proinflammatory properties and also inhibit cell cycle progression of hematopoietic stem cells. Characteri zation of MIP-1 alpha receptor(s) has been confused because of its rep orted aggregation to inactive forms. Using a defined monomeric form of MIP-1 alpha that is biologically active for stem cell inhibition and induction of oxidative metabolism in polymor-phonuclear cells, we repo rt the detection of high- and low-affinity receptor classes on human l eukemic CD34(+) blast cells, promyelocytic cells, monocytes, periphera l blood neutrophils, and T cells. Both high- and low-affinity classes are expressed simultaneously in promyelocytes and neutrophils. The cal culated kd for high-affinity receptors correlates with the concentrati ons of MIP-1 alpha required to induce a biologic effect on stem cells and neutrophils. Cross-linking studies show that MIP-1 alpha associate s with two cell surface proteins with apparent molecular masses of 92 kD and 52 kD. Direct competition binding studies combined with studies on the inhibition of stem cells show that human and murine MIP-1 alph a have different receptor-binding and biologic properties. (C) 1994 by The American Society of Hematology.