Macrophage inflammatory protein-1alpha uses a novel receptor for primitive hemopoietic cell inhibition.
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.
Ottersbach
K
K
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, Scotland.
Cook
D N
DN
Kuziel
W A
WA
Humbles
A
A
Lu
B
B
Gerard
C
C
Proudfoot
A E
AE
Graham
G J
GJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division / Q000187:drug effects*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000172:deficiency / Q000502:physiology*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; C080633:macrophage inflammatory protein 1alpha receptor