The active monomeric form of macrophage inflammatory protein-1α interacts with high- and low-affinity classes of receptors on human hematopoietic cells

Abstract

Macrophage inflammatory protein-1α (MIP-1α) and its human homologue GOS19.1/LD78 are members of the C-C chemokine/intercrine family of secreted proteins. They have proinflammatory properties and also inhibit cell cycle progression of hematopoietic stem cells. Characterization of MIP-1α receptor(s) has been confused because of its reported aggregation to inactive forms. Using a defined monomeric form of MIP-1α that is biologically active for stem cell inhibition and induction of oxidative metabolism in polymorphonuclear cells, we report the detection of high- and low-affinity receptor classes on human leukemic CD34+ blast cells, promyelocytic cells, monocytes, peripheral blood neutrophils, and T cells. Both high- and low- affinity classes are expressed simultaneously in promyelocytes and neutrophils. The calculated kd for high-affinity receptors correlates with the concentrations of MIP-1α required to induce a biologic effect on stem cells and neutrophils. Cross-linking studies show that MIP-1α associates 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-1α have different receptor-binding and biologic properties.