MACROPHAGE INFLAMMATORY PROTEIN - ITS CHARACTERISTICS, BIOLOGICAL PROPERTIES AND ROLE IN THE REGULATION OF HEMATOPOIESIS

Studies on haemopoietic stem cells had led to the realisation that neg ative feedback inhibitors play an important role in regulating their p roliferation. One such molecule was identified as MIP-1alpha. One of a family of cytokines, originally recognised as inflammatory molecules, MIP-1alpha is now potentially valuable as a means of manipulating and protecting haemopoietic (and possibly other) stem cells during chemot herapy. This short review briefly considers the structural classificat ion of MIP-1alpha and its molecular relatives and indicates some of th e probable human/murine equivalent molecules outlining the evidence fo r the equivalence of MIP-1alpha (murine) and LD78 (human). Sources of MIP-1alpha/LD78 are identified as monocyte/macrophage and lymphocytic cells and their role in inflammatory responses is seen to be significa nt. All proliferation in haemopoietic tissue is now recognised as a ma jor target for MIP-1alpha action. In vitro it synergises with certain growth factors to promote progenitor cell colony formation, but effect s are dependent on the maturational age of the cells promoted. With mo re primitive cells it is seen as inhibitory. This property is particul arly valuable in vivo where MIP-1alpha can protect stem cells against the effects of cytotoxic agents. Since it appears that leukaemic stem cell proliferation is not inhibited, MIP-1alpha/LD78 present great pot ential for stem cell protection in the theatre of cytotoxic therapies.