Peled A, Gonzalo J A, Lloyd C, Gutierrez-Ramos J C
The Center for Blood Research, Inc, Boston, MA, USA.
Blood. 1998 Mar 15;91(6):1909-16.
During inflammatory processes, inflamed tissues signal the bone marrow (BM) to produce more mature leukocytes in ways that are not yet understood. We report here that, during the development of lung allergic inflammation, the administration of neutralizing antibodies to the chemotactic cytokine, Eotaxin, prevented the increase in the number of myeloid progenitors produced in the BM, therefore reducing the output of mature myeloid cells from BM. Conversely, the in vivo administration of Eotaxin increased the number of myeloid progenitors present in the BM. Furthermore, we found that, in vitro, Eotaxin is a colony-stimulating factor for granulocytes and macrophages. Eotaxin activity synergized with stem cell factor but not with interleukin-3 or granulocyte-macrophage colony-stimulating factor and was inhibited by pertussis toxin. We report also that CCR-3, the receptor for Eotaxin, was expressed by hematopoietic progenitors (HP). Thus, during inflammation, Eotaxin acts in a paracrine way to shift the differentiation of BM HP towards the myeloid lineage.
在炎症过程中,发炎组织向骨髓(BM)发出信号,促使其产生更多成熟白细胞,但其具体机制尚不清楚。我们在此报告,在肺部过敏性炎症发展过程中,给予趋化细胞因子嗜酸性粒细胞趋化因子(Eotaxin)的中和抗体可阻止骨髓中产生的髓系祖细胞数量增加,从而减少骨髓中成熟髓系细胞的输出。相反,在体内给予嗜酸性粒细胞趋化因子会增加骨髓中髓系祖细胞的数量。此外,我们发现,在体外,嗜酸性粒细胞趋化因子是粒细胞和巨噬细胞的集落刺激因子。嗜酸性粒细胞趋化因子的活性与干细胞因子协同作用,但与白细胞介素-3或粒细胞-巨噬细胞集落刺激因子无协同作用,且被百日咳毒素抑制。我们还报告称,嗜酸性粒细胞趋化因子的受体CCR-3由造血祖细胞(HP)表达。因此,在炎症过程中,嗜酸性粒细胞趋化因子以旁分泌方式发挥作用,使骨髓造血祖细胞的分化向髓系谱系转变。