Polymerization of murine macrophage inflammatory protein 1 alpha inactivates its myelosuppressive effects in vitro: the active form is a monomer.
Macrophage inflammatory protein (MIP) 1 alpha has myelosuppressive and myeloprotective activity. That MIP-1 alpha polymerizes is known; this phenomenon was evaluated in terms of myelosuppression by assessing the effects of recombinant murine MIP-1 alpha 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-1 alpha is the active suppressive form for myeloid progenitor cells in vitro. (iii) Polymerized MIP-1 alpha is inactive and does not interfere with suppression by monomeric MIP-1 alpha. (iv) MIP-1 alpha has approximately 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-1 alpha might be a control mechanism that limits the myelosuppressive effects of monomeric MIP-1 alpha.
Mantel
C
C
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Kim
Y J
YJ
Cooper
S
S
Kwon
B
B
Broxmeyer
H E
HE
D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002850:Chromatography, Gel; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D015846:Monokines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D013936:Thymidine