Polymerization of murine macrophage inflammatory protein 1α inactivates its myelosuppressive effects in vitro: The active form is a monomer

Charlie Mantel, Young J. Kim, Scott Cooper, Byoung Kwon, Hal E. Broxmeyer

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44 Scopus citations

Abstract

Macrophage inflammatory protein (MIP) 1α has myelosuppressive and myeloprotective activity. That MIP-1α polymerizes is known; this phenomenon was evaluated in terms of myelosuppression by assessing the effects of recombinant murine MIP-1α 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-1α is the active suppressive form for myeloid progenitor cells in vitro. (iii) Polymerized MIP-1α is inactive and does not interfere with suppression by monomeric MIP-1α. (iv) MIP-1α has ≈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-1α might be a control mechanism that limits the myelosuppressive effects of monomeric MIP-1α.

Original languageEnglish (US)
Pages (from-to)2232-2236
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number6
DOIs
StatePublished - Mar 15 1993

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