Broxmeyer H E, Youn B S, Kim C, Hangoc G, Cooper S, Mantel C
Departments of Microbiology and Immunology, and Medicine (Hematology/Oncology), the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, Indiana 46202, USA.
Ann N Y Acad Sci. 2001 Jun;938:117-27; discussion 127-8. doi: 10.1111/j.1749-6632.2001.tb03580.x.
Chemokines have been implicated in regulation of various aspects of hematopoiesis, including negative regulation of the proliferation of immature subsets of myeloid progenitor cells (MPCs), chemotaxis of MPCs, and survival enhancement of MPCs after delayed growth factor addition. Since chemokine receptors are seven-transmembrane-spanning G-protein-linked receptors and the chemotactic effect in vitro of the CXC chemokine SDF-1 is pertussis toxin (PT)-sensitive, implying the involvement of G alpha i proteins as mediators of SDF-1-induced chemotaxis, we evaluated the effects of PT on other chemokine actions influencing MPCs. While the in vitro survival-enhancing effects of SDF-1 on GM-CSF and steel factor-dependent mouse bone marrow granulocyte macrophage progenitors (CFU-GM) were pertussis toxin-sensitive, the suppressive effects of the CC chemokine MIP-1 alpha and the CXC chemokine IL-8 on colony formation by GM-CSF and steel factor-sensitive CFU-GM were insensitive to pertussis toxin. These results suggest that not all chemokine-mediated effects on MPCs are necessarily mediated through pertussis toxin-sensitive G alpha i proteins.
趋化因子参与了造血过程各个方面的调节，包括对髓系祖细胞（MPC）未成熟亚群增殖的负调控、MPC的趋化作用以及在延迟添加生长因子后MPC存活的增强。由于趋化因子受体是七次跨膜的G蛋白偶联受体，且CXC趋化因子SDF-1在体外的趋化作用对百日咳毒素（PT）敏感，这意味着Gαi蛋白作为SDF-1诱导趋化作用的介质参与其中，我们评估了PT对影响MPC的其他趋化因子作用的影响。虽然SDF-1对GM-CSF和Steel因子依赖的小鼠骨髓粒巨噬祖细胞（CFU-GM）的体外存活增强作用对百日咳毒素敏感，但CC趋化因子MIP-1α和CXC趋化因子IL-8对GM-CSF和Steel因子敏感的CFU-GM集落形成的抑制作用对百日咳毒素不敏感。这些结果表明，并非所有趋化因子对MPC的介导作用都必然通过百日咳毒素敏感的Gαi蛋白介导。
