Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1α

R. Maze, B. Sherry, B. S. Kwon, A. Cerami, H. E. Broxmeyer

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64 Scopus citations

Abstract

Purified recombinant murine macrophage inflammatory protein-1α (rmuMIP-1α), a cytokine with myelopoietic activity in vitro, was assessed in vivo by injection into C3H/HeJ mice for effects on proliferation (percentage of cells in S phase DNA synthesis of the cell cycle) and absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the femur and spleen, and on nucleated cellularity in the bone marrow, spleen, and blood. rmuMIP-1α rapidly decreased cycling rates (at 2 to 10 μg/mouse i.v.) and absolute numbers (at 5 to 10 μg/mouse i.v.) of myeloid progenitor cells in the marrow and spleen. These effects were dose-and time-dependent and reversible. Suppressive effects were noted within 3 to 24 h for cell cycling and absolute numbers of progenitor cells in the marrow and spleen, and by 48 h for circulating neutrophils. A study comparing the effects of i.v. injection of rmuMIP-1α versus rmuMIP-1β, a biochemically similar molecule but with no myelosuppressive effects in vitro, demonstrated myelosuppression in vivo by rmuMIP-1α, but not by rmuMIP-1β. The results suggest that rmuMIP-1α has myelosuppressive activity in vivo and offers the possibility that it may be a useful adjunct to treatments involving cytotoxic drugs because of its reversible suppressive effects on normal progenitor cell cycling.

Original languageEnglish (US)
Pages (from-to)1004-1009
Number of pages6
JournalJournal of Immunology
Volume149
Issue number3
StatePublished - 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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