POLYMERIZATION OF MURINE MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA INACTIVATES ITS MYELOSUPPRESSIVE EFFECTS INVITRO - THE ACTIVE FORM IS A MONOMER

Macrophage inflammatory protein (MIP) 1alpha has myelosuppressive and myeloprotective activity. That MIP-1alpha polymerizes is known; this phenomenon was evaluated in terms of myelosuppression by assessing the effects of recombinant murine MIP-1alpha on colony formation of murine and human myeloid progenitor cells in vitro. The following results are reported: (i) Polymerization is diluent- and concentration-dependent. (ii) Monomeric MIP-1alpha is the active suppressive form for myeloid progenitor cells in vitro. (iii) Polymerized MIP-1alpha is inactive and does not interfere with suppression by monomeric MIP-1alpha. (iv) MIP-1alpha has almost-equal-to 1000-fold higher specific activity than has been reported, but its effects are still specific for immature subsets of myeloid progenitors. (v) Suppression is initiated during the DNA-synthesis phase of the cell cycle. We conclude that polymerization of MIP-1alpha might be a control mechanism that limits the myelosuppressive effects of monomeric MIP-1alpha.