Numerous growth factors, cytokines, and chemokines are secreted by human CD34+ cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner
Numerous growth factors, cytokines, and chemokines are secreted by human CD34+ cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner
复制标题
DOI：
10.1182/blood.v97.10.3075
复制
发表时间：
2001-05-15
期刊：
影响因子：
20.3
通讯作者：
Ratajczak, MZ
中科院分区：
文献类型：
--
作者：
Majka, M;Janowska-Wieczorek, A;Ratajczak, MZ
这项研究的目的是进一步探讨以下假设：正常人造血的早期阶段可能是由自分泌/旁分泌调节环和早期造血细胞中的串扰来策略的。高度纯化的正常人CD34（+）细胞和离体扩展了早期菌落形成单位颗粒细胞巨噬细胞（CFU-GM）衍生的，爆发的形成单位 - 雌激素（BFU-E）衍生的和CFU-Megakaryocyte（CFU--熟型） MEG）衍生的细胞被表型用于Messenger RNA表达和各种生长因子，细胞因子和趋化因子确定该分泌的生物学意义。发现了许多生长因子（试剂配体[KIL]，FLT3配体，成纤维细胞生长因子-2 [FGF-2]，血管内皮生长因子[VEGF]，肝细胞生长因子[HGF]，胰岛细胞生长因子[HGF]，胰岛素样生长因子1 [IGF [IGF）[IGF [IGF）[IGF -1]和血小板蛋白[TPO]）;细胞因子（肿瘤坏死因子-Alpha，FAS配体，干扰素α，白介素1 [IL-1]和IL-16）；和趋化因子（巨噬细胞炎性蛋白-1α[MIP-1α]，MIP-1β，受激活调节，正常T细胞表达和分泌[Rantes]，单核细胞趋化蛋白3 [MCP-3]，MCP-4，MCP-4，MCP-4， IL-8，干扰素诱导蛋白10，巨噬细胞衍生的趋化因子[MDC]和血小板因子-4 [PF-4]）由CD34（+）细胞表达。更重要的是，调节蛋白VEGF，HGF，FGF-2，KL，FLT3配体，TPO，IL-16，IGF-1，转化生长因子-BETA1（TGF-BETA1）（TGF-BETA1），TGF-BETA2，TGF-BETA2，RANTES，RANTES，RANTES，MIP-1 ALPHA，MIP-1 ALPHA在由这些细胞调节的培养基中鉴定出，MIP-1β，IL-8和PF-4。此外，发现由CD34（+）细胞来调节的培养基抑制凋亡，并稍微刺激其他新鲜分离的CD34（+）细胞的增殖。化学cfu-gm和CFU-meg衍生的细胞以及其他CD34（+）细胞；最后，刺激人内皮细胞的增殖。还证明，这些各种造血生长因子，细胞因子和趋化因子由CFU-GM-，CFU-MEG-和BFU-E衍生的细胞表达和分泌。得出的结论是，正常的人类CD34（+）细胞和造血前体分泌了许多调节分子，这些调节分子构成了细胞间跨言式网络的基础，并以自分泌和/或旁分泌方式调节正常人血肿的各个阶段。 （Blood。2001; 97：3075-3085）（C）2001年美国血液学学会。
The aim of this study was to explore further the hypothesis that early stages of normal human hematopoiesis might be coregulated by autocrine/paracrine regulatory loops and by cross-talk among early hematopoietic cells. Highly purified normal human CD34(+) cells and ex vivo expanded early colony-forming unit-granulocyte-macrophage (CFU-GM)-derived, burst forming unit-erythroid (BFU-E)-derived, and CFU-megakaryocyte (CFU-Meg)-derived cells were phenotyped for messenger RNA expression and protein secretion of various growth factors, cytokines, and chemokines to determine the biological significance of this secretion. Transcripts were found for numerous growth factors (kit ligand [KIL], FLT3 ligand, fibroblast growth factor-2 [FGF-2], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], insulinlike growth factor-1 [IGF-1], and thrombopoietin [TPO]); cytokines (tumor necrosis factor-alpha, Fas ligand, interferon alpha, interleukin 1 [IL-1], and IL-16); and chemokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], MIP-1 beta, regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-3 [MCP-3], MCP-4, IL-8, interferon-inducible protein-10, macrophage-derived chemokine [MDC], and platelet factor-4 [PF-4]) to be expressed by CD34(+) cells. More importantly, the regulatory proteins VEGF, HGF, FGF-2, KL, FLT3 ligand, TPO, IL-16, IGF-1, transforming growth factor-beta1 (TGF-beta1), TGF-beta2, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, and PF-4 were identified in media conditioned by these cells. Moreover, media conditioned by CD34(+) cells were found to inhibit apoptosis and slightly stimulate the proliferation of other freshly isolated CD34(+) cells; chemo-attract CFU-GM- and CFU-Meg-derived cells as well as other CD34(+) cells; and, finally, stimulate the proliferation of human endothelial cells. It was also demonstrated that these various hematopoietic growth factors, cytokines, and chemokines are expressed and secreted by CFU-GM-, CFU-Meg-, and BFU-E-derived cells. It is concluded that normal human CD34(+) cells and hematopoietic precursors secrete numerous regulatory molecules that form the basis of intercellular cross-talk networks and regulate in an autocrine and/or a paracrine manner the various stages of normal human hematopoiesis. (Blood. 2001;97:3075-3085) (C) 2001 by The American Society of Hematology.