Macrophage inflammatory protein-1α uses a novel receptor for primitive hemopoietic cell inhibition

Abstract

Macrophage inflammatory protein-1α (MIP-1α) is a member of the chemokine family of proinflammatory mediators. In addition to its inflammatory roles, MIP-1α has been shown to be active as an inhibitor of primitive hemopoietic cell proliferation. Indeed, a dysfunction in this inhibitory process has been postulated to contribute to leukemogenesis. Research has been aimed at characterizing the receptor involved in cellular inhibition by MIP-1α. This study demonstrates that of all the β-chemokines tested, only MIP-αis capable of inhibiting primitive hemopoletic cell proliferation. Because no MIP-1αspecific receptors have been identified, this suggests that inhibition is mediated by an uncharacterized receptor. Further evidence for the involvement of a novel receptor in this process is the equivalent potencies of MIP-1αS and MIP-1αP variants of human MIP-1α and the fact that primitive cells from bone marrow derived from individual MIP-1α receptor null mice display a full response to MIP-1α inhibition. © 2001 by The American Society of Hematology.