Mantel C, Kim Y J, Cooper S, Kwon B, Broxmeyer H E
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2232-6. doi: 10.1073/pnas.90.6.2232.
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.
巨噬细胞炎性蛋白（MIP）-1α具有骨髓抑制和骨髓保护活性。已知MIP-1α会发生聚合；通过评估重组鼠MIP-1α对体外培养的鼠和人髓系祖细胞集落形成的影响，从骨髓抑制方面对这一现象进行了评估。报告结果如下：（i）聚合作用取决于稀释剂和浓度。（ii）单体MIP-1α是体外髓系祖细胞的活性抑制形式。（iii）聚合的MIP-1α无活性，且不干扰单体MIP-1α的抑制作用。（iv）MIP-1α的比活性比已报道的高约1000倍，但其作用仍对髓系祖细胞的未成熟亚群具有特异性。（v）抑制作用在细胞周期的DNA合成期开始。我们得出结论，MIP-1α的聚合可能是一种控制机制，可限制单体MIP-1α的骨髓抑制作用。
