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

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of the chemokine family of proinflammatory mediators. In addition to its inflammatory roles, MIP-1 alpha 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-1 alpha. This study demonstrates that of all the beta -chemokines tested, only MIP-1 alpha is capable of inhibiting primitive hemopoietic cell proliferation. Because no MIP-1 alpha -specific 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-1 alphaS and MIP-1 alphaP variants of human MIP-1 alpha and the fact that primitive cells from bone marrow derived from individual MIP-1 alpha receptor null mice display a full response to MIP-1 alpha inhibition. (Blood. 2001;98:3476-3478) (C) 2001 by The American Society of Hematology.