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

Rodney Maze, Barbara Sherry, Byoung S. Kwon, Anthony Cerami, Hal Broxmeyer

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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
Pages (from-to)1004-1009
Number of pages6
JournalJournal of Immunology
Volume149
Issue number3
StatePublished - Aug 1 1992

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Macrophage Inflammatory Proteins
Spleen
Bone Marrow
Stem Cells
Myeloid Progenitor Cells
Erythroid Precursor Cells
Injections
Inbred C3H Mouse
S Phase
Granulocytes
Femur
Cell Cycle
Neutrophils
Macrophages
Cell Proliferation
Cytokines
DNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1α. / Maze, Rodney; Sherry, Barbara; Kwon, Byoung S.; Cerami, Anthony; Broxmeyer, Hal.

In: Journal of Immunology, Vol. 149, No. 3, 01.08.1992, p. 1004-1009.

Research output: Contribution to journalArticle

Maze, Rodney ; Sherry, Barbara ; Kwon, Byoung S. ; Cerami, Anthony ; Broxmeyer, Hal. / Myelosuppressive effects in vivo of purified recombinant murine macrophage inflammatory protein-1α. In: Journal of Immunology. 1992 ; Vol. 149, No. 3. pp. 1004-1009.
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