|Title||Macrophage inflammatory protein-1alpha uses a novel receptor for primitive hemopoietic cell inhibition.|
|Publication Type||Journal Article|
|Year of Publication||2001|
|Authors||Ottersbach K, Cook DN, Kuziel WA, Humbles A, Lu B, Gerard C, Proudfoot AE, Graham GJ|
|Date Published||2001 Dec 1|
|Keywords||Animals, Bone Marrow Cells, Cell Division, Chemokine CCL3, Chemokine CCL4, Hematopoietic Stem Cells, Macrophage Inflammatory Proteins, Mice, Mice, Knockout, Receptors, Chemokine|
Macrophage inflammatory protein-1alpha (MIP-1alpha) is a member of the chemokine family of proinflammatory mediators. In addition to its inflammatory roles, MIP-1alpha 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-1alpha. This study demonstrates that of all the beta-chemokines tested, only MIP-1alpha is capable of inhibiting primitive hemopoietic cell proliferation. Because no MIP-1alpha-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-1alphaS and MIP-1alphaP variants of human MIP-1alpha and the fact that primitive cells from bone marrow derived from individual MIP-1alpha receptor null mice display a full response to MIP-1alpha inhibition.