Joshi S S, Connolly J, Mann S L, Sharp J G
Department of Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha 68198-6395, USA.
Exp Hematol. 1995 Nov;23(12):1284-8.
Cell-surface molecules, particularly glycoconjugates, appear to be involved in the in vivo homing of hematopoietic stem and progenitor cells and in their interactions with hematopoietic stromal cells. To study the role of cell-surface molecules of hematopoietic stem cells, the expression of some surface molecules was altered using n-butanol treatment. We examined the in vivo and in vitro colony-forming abilities, in vivo homing patterns, and cell-surface lectin receptor expression of butanol-treated bone marrow cells (BMC) from BDF1 mice. The butanol-treated/-modified BMC formed an increased number of significantly larger spleen colonies (CFU-S) in lethally irradiated (1050 rad) mice. The butanol-treated BM formed significantly larger in vitro granulocyte-macrophage progenitor cell colonies (CFU-C) and in vitro fibroblastic colonies (CFU-F), although the number of such colonies was not significantly altered. The homing pattern of butanol-treated BMC was studied by comparing the distribution in lethally irradiated mice of intravenously injected 51Cr-labeled butanol-treated BMC with that of untreated cells. The butanol treatment altered the in vivo homing pattern of these cells, with increased homing to liver, spleen, and bone marrow and decreased homing to thymus, lung, and mesenteric lymph nodes. Flow-cytometric analyses of butanol-treated BMC showed an increased expression of receptors for the lectins concanavalin A (conA) and wheat germ agglutinin (WGA), indicating an increased expression of mannosyl and galactosyl residues, which are known sugar moieties in hematopoietic stem/progenitor cell homing. These results indicate that cell surface modifications can influence homing and growth of transplanted BMC and that butanol treatment is a useful tool for studying the mechanisms of hematopoietic stem/progenitor cell homing in vivo and for further characterizing the molecules involved in this process.
细胞表面分子,尤其是糖缀合物,似乎参与了造血干细胞和祖细胞在体内的归巢过程以及它们与造血基质细胞的相互作用。为了研究造血干细胞表面分子的作用,使用正丁醇处理改变了一些表面分子的表达。我们检测了来自BDF1小鼠的经正丁醇处理的骨髓细胞(BMC)的体内和体外集落形成能力、体内归巢模式以及细胞表面凝集素受体表达。经正丁醇处理/修饰的BMC在接受致死剂量照射(1050拉德)的小鼠中形成的脾集落(CFU-S)数量增加且明显更大。经正丁醇处理的骨髓形成的体外粒细胞-巨噬细胞祖细胞集落(CFU-C)和体外成纤维细胞集落(CFU-F)明显更大,尽管此类集落的数量没有显著改变。通过比较静脉注射51Cr标记的经正丁醇处理的BMC与未处理细胞在接受致死剂量照射小鼠中的分布情况,研究了经正丁醇处理的BMC的归巢模式。正丁醇处理改变了这些细胞的体内归巢模式,使其归巢至肝脏、脾脏和骨髓的比例增加,而归巢至胸腺、肺和肠系膜淋巴结的比例降低。对经正丁醇处理的BMC进行的流式细胞术分析显示,伴刀豆球蛋白A(conA)和麦胚凝集素(WGA)凝集素的受体表达增加,表明甘露糖基和半乳糖基残基的表达增加,这些是造血干/祖细胞归巢中已知的糖部分。这些结果表明,细胞表面修饰可影响移植的BMC的归巢和生长,正丁醇处理是研究造血干/祖细胞体内归巢机制以及进一步鉴定参与该过程的分子的有用工具。