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1.
Minami A Tsuboi I Harada T Fukumoto T Hiramoto M Koshinaga M Hirabayashi Y Kanno J Inoue T Aizawa S 《Experimental biology and medicine (Maywood, N.J.)》2007,232(1):134-145
Neopterin is produced by monocytes and is a useful biomarker of inflammatory activation. We found that neopterin enhanced in vivo and in vitro granulopoiesis triggered by the stromal-cell production of cytokines in mice. The effects of neopterin on B lymphopoiesis during the enhancement of granulopoiesis were determined using the mouse model of senescent stromal-cell impairment (SCI), a subline of senescence-accelerated mice (SAM). In non-SCI mice (a less senescent stage of SCI mice), treatment with neopterin decreased the number of colonies, on a semisolid medium, of colony-forming units of pre-B-cell progenitors (CFU-preB) from unfractionated bone marrow (BM) cells, but not that from a population rich in pro-B and pre-B cells without stromal cells. Neopterin upregulated the expression of genes for the negative regulators of B lymphopoiesis such as tumor necrosis factor-alpha (TNF-alpha ), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in cultured stromal cells, implying that neopterin suppressed the CFU-preB colony formation by inducing negative regulators from stromal cells. The intraperitoneal injection of neopterin into non-SCI mice resulted in a marked decrease in the number of femoral CFU-preB within 1 day, along with increases in TNF-alpha and IL-6 expression levels. However, in SCI mice, in vivo and in vitro responses to B lymphopoiesis and the upregulation of cytokines after neopterin treatment were less marked than those in non-SCI mice. These results suggest that neopterin predominantly suppressed lymphopoiesis by inducing the production of negative regulators of B lymphopoiesis by stromal cells, resulting in the selective suppression of in vivo B lymphopoiesis. These results also suggest that neopterin facilitated granulopoiesis in BM by suppressing B lymphopoiesis, thereby contributing to the potentiation of the inflammatory process; interestingly, such neopterin function became impaired during senescence because of attenuated stromal-cell function, resulting in the downmodulation of the host-defense mechanism in the aged. 相似文献
2.
在无外源刺激条件征,我室所建小鼠胎肝基质细胞系MFLC可自发分泌多处类型细胞因子,其中IL-6及化学趋化因了水平较高,GM-CSF较低,但示检测到IL-3及IL-7活性,引细胞上清对小鼠骨髓造血干细胞有明显的促集落形成效应。并呈现剂量依赖关系,所形成的集落以CFU-GMM及CFU-GM为主,此细胞上清还促进5-Fu耐受小鼠骨髓造血干细胞的集落形成,提示上清中存在SCF样活性成份。上述结果表明,MF 相似文献
3.
Mansour A Anginot A Mancini SJ Schiff C Carle GF Wakkach A Blin-Wakkach C 《Cell research》2011,21(7):1102-1115
B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity. 相似文献
4.
人参总皂甙对人GM-CSF和GM-CSFR表达的调控 总被引:6,自引:0,他引:6
为探讨人参调控粒细胞发生的生物学机制,采用造血祖细胞和骨髓基质细胞体外培养、造血生长因子生物学活性检测、免疫细胞化学、核酸分子原位杂交、免疫沉淀和蛋白印迹等现代生物学技术,研究人参总皂甙(total saponins of Panax ginaeng,TSPG)对人粒-巨噬细胞集落刺激因子(granulocyte-macrophage colony-stimulating factor,GM-CSF)和粒-巨噬细胞集落刺激因子受体α(GM-CSFRα)表达的影响。结果:(1)经TSPG(50μg/m1)诱导制备的骨髓基质细胞、胸腺细胞、脾细胞、血管内皮细胞和单核细胞条件培养液可显著提高粒单系造血祖细胞(CFU-GM)的集落产率;(2)经TSPG(50μg/ml)诱导后,上述细胞的GM-CSF蛋白(诱导24h)和mRNA(诱导12h)表达显著提高;(3)经TSPG(50μg/ml)诱导24h骨髓造血细胞的GM-CSFRα蛋白表达增强;(4)经TSPG(50μg/ml)刺激后2min,GM-CSFRα和Shc发生酪氨酸磷酸化,5min时达高峰,随后去磷酸化。上述结果表明,TSPG可能通过直接和/或间接途径促进淋巴细胞与骨髓基质细胞合成与分泌GM-CSF,诱导骨髓造血细胞表达GM-CSFRα,并刺激GM-CSFRα和Shc的酪氨酸可逆磷酸化,从而通过调控GM-CSF的信号转导过程,促进CFU-GM的增殖。 相似文献
5.
In this study, we have demonstrated that Korean Panax ginseng (KG) significantly enhances myelopoiesis in vitro and reconstitutes bone marrow after 5-flurouracil-induced (5FU) myelosuppression in mice. KG promoted total white blood cell, lymphocyte, neutrophil and platelet counts and improved body weight, spleen weight, and thymus weight. The number of CFU-GM in bone marrow cells of mice and serum levels of IL-3 and GM-CSF were significantly improved after KG treatment. KG induced significant c-Kit, SCF and IL-1 mRNA expression in spleen. Moreover, treatment with KG led to marked improvements in 5FU-induced histopathological changes in bone marrow and spleen, and partial suppression of thymus damage. The levels of IL-3 and GM-CSF in cultured bone marrow cells after 24 h stimulation with KG were considerably increased. The mechanism underlying promotion of myelopoiesis by KG was assessed by monitoring gene expression at two time-points of 4 and 8 h. Treatment with Rg1 (0.5, 1 and 1.5 μmol) specifically enhanced c-Kit, IL-6 and TNF-α mRNA expression in cultured bone marrow cells. Our results collectively suggest that the anti-myelotoxicity activity and promotion of myelopoiesis by KG are mediated through cytokines. Moreover, the ginsenoside, Rg1, supports the role of KG in myelopoiesis to some extent. 相似文献
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在无外源刺激条件下,我室所建小鼠胎肝基质细胞系MFLC可自发分泌多种类型细胞因子,其中IL-6及化学趋化因子水平较高,GM-CSF水平较低,但未检测到IL-3及IL-7活性。此细胞上清对小鼠骨髓造血干细胞有明显的促集落形成效应,并呈现剂量依赖关系,所形成的集落以CFU-GMM及CFU-GM为主;此细胞上清还促进5-Fu耐受小鼠骨髓造血干细胞的集落形成,提示上清中存在SCF样活性成份。上述结果表明,MFLC的建立有利于分析干细胞在胎肝内如何向pro-T细胞分化发育的机理并有利于阐明细胞因子网络调节在其中的作用。 相似文献
8.
The induction of lymphokine synthesis and cell growth in IL 3-dependent cell lines using antigen-antibody complexes 总被引:5,自引:0,他引:5
G S Le Gros J E Le Gros J D Watson 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(2):422-428
Several IL 3-dependent murine bone marrow-derived cell lines can be stimulated to grow with antigen-antibody (Ag.Ab) complexes. The Ag.Ab complexes induced lymphokine gene expression and the synthesis of IL 2, GM-CSF, IL 3, and BSF-1 (IL 4). The lymphokines produced by these IL 3-dependent cells appeared to stimulate their own growth, as both IL 3 and BSF-1 (IL 4) stimulated the growth of IL 3-dependent cells. Ag.Ab complexes also stimulate the growth of primary cultures of bone marrow cells that have been previously activated with IL 3. Normal bone marrow, IL 2-, and GM-CSF-dependent bone marrow cell lines could bind Ag.Ab complexes, but binding did not result in the induction of lymphokine synthesis or cell growth. Hyperimmune serum from mice also stimulated lymphokine synthesis and cell growth in IL 3-dependent cells, and the stimulatory activity was removed by treatment with Staphylococcus aureus protein A, suggesting the presence of Ag.Ab complexes. 相似文献
9.
Urdziková L Likavčanová-Mašínová K Vaněček V Růžička J Sedý J Syková E Jendelová P 《Cytotherapy》2011,13(9):1090-1104
Background aimsThe effect of granulocyte–colony-stimulating factor (G-CSF) and/or the cytokine fms-like thyrosin kinase 3 (Flt3) ligand on functional outcome and tissue regeneration was studied in a rat model of spinal cord injury (SCI).MethodsRats with a balloon-induced compression lesion were injected with G-CSF and/or Flt3 ligand to mobilize bone marrow cells. Behavioral tests (Basso-Beattie-Bresnahan and plantar test), blood counts, morphometric evaluation of the white and gray matter, and histology were performed 5 weeks after SCI.ResultsThe mobilization of bone marrow cells by G-CSF, Flt3 ligand and their combination improved the motor and sensory performance of rats with SCI, reduced glial scarring, increased axonal sprouting and spared white and gray matter in the lesion. The best results were obtained with a combination of G-CSF and Flt3. G-CSF alone or in combination with Flt3 ligand significantly increased the number of white blood cells, but not red blood cells or hemoglobin content, during and after the time–course of bone marrow stimulation. The combination of factors led to infiltration of the lesion by CD11b+ cells.ConclusionsThe observed improvement in behavioral and morphologic parameters and tissue regeneration in animals with SCI treated with a combination of both factors could be associated with a prolonged time–course of mobilization of bone marrow cells. The intravenous administration of G-CSF and/or Flt3 ligand represents a safe and effective treatment modality for SCI. 相似文献
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K M McNagny P A Cazenave M D Cooper 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(8):2551-2556
To explore the cell surface molecules expressed on pre-B cells we have produced a panel of alloantibodies against transformed pre-B cells from BALB/c mice by immunizing a wild mouse, Mus spretus. One of these antibodies, BP-3, recognized glycoproteins of Mr 38,000 to 48,000 on pre-B cells transformed either by the Abelson murine leukemia virus or an erb B oncogene construct. Removal of N-linked oligosaccharides from the BP-3 Ag revealed a single core protein of Mr 32,000. The Ag was expressed by bone marrow cells in all but one (A/J) of the inbred mouse strains tested and in wild mice of biochemical groups Mus-1 and Mus-2. Analysis of the tissue distribution revealed expression of the BP-3 reactive molecule on normal pre-B and B cells in the bone marrow, 35% of B cells in the circulation, 30% of the B cells in the spleen, and less than or equal to 20% of B cells in lymph nodes, peritoneal cavity, and Peyer's patches. The subpopulation of BP-3+ B cells in bone marrow and peripheral tissues displayed an immature phenotype (IgM IgD +/- ). Examination of a panel of transformed B lineage cells confirmed the early stage-specific expression of the BP-3 alloantigen. In addition, a myeloid cell line and normal myeloid cells were found to express the BP-3 alloantigen. In contrast to B lineage cells, the level of BP-3 expression increased as a function of myeloid cell differentiation. Myeloid cells in the bone marrow expressed relatively little Ag, whereas circulating neutrophils and peritoneal macrophages expressed relatively high levels of the BP-3 alloantigen with Mr 38,000, 41,000, and 46,000. The data suggest that this variably glycosylated cell surface protein could play different roles in the differentiation of B lineage and myeloid lineage cells. The BP-3 alloantigen appears to be a useful marker for virgin B cells that have recently migrated from the bone marrow to the periphery. 相似文献
12.
Yan Hu Xiaoqun Li Xin Zhi Wei Cong Biaotong Huang Huiwen Chen Yajun Wang Yinghua Li Lipeng Wang Chao Fang Jiawei Guo Ying Liu Jin Cui Liehu Cao Weizong Weng Qirong Zhou Sicheng Wang Xiao Chen Jiacan Su 《EMBO reports》2021,22(7)
Receptor activator of NF‐κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter‐driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)‐induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss. 相似文献
13.
Bone marrow lineage-negative (Lin(-)) c-Kit(+) Sca-1(+) hematopoietic cells from human GM-CSF receptor gene transgenic mice were cultured on established bone marrow stromal cell (TBR59) layers and on semisolid medium. In the semisolid assay, an increasing number of larger colonies were observed in the presence of hGM-CSF. By coculture with the stromal cells, cobblestones containing myeloid and lymphoid lineages of cells were formed from the stem cell enriched fraction, and addition of hGM-CSF strongly stimulated formation of the cobblestones containing both lineages. Repeating passages of the cobblestones on TBR59 stromal cells in the presence of hGM-CSF gradually decreased cobblestone formation and inversely increased macrophages and granulocytes, while mast cells were generated when the cells derived from the semisolid assay were cultured in a liquid medium containing hGM-CSF. These results consistently suggest that cytokines such as GM-CSF may costimulate the immature hematopoietic cells at their stroma-dependent phase before lineage commitment, and after commitment that occurs by an intrinsic program of the cells, they may stimulate maintenance and maturation of progenitor cells. 相似文献
14.
Stephen E. Haynesworth Marilyn A. Baber Arnold I. Caplan 《Journal of cellular physiology》1996,166(3):585-592
We previously reported the purification, culture-expansion, and osteogenic differentiation potential of mesenchymal progenitor cells (MPCs) derived from human bone marrow. As a first step to establishing the phenotypic characteristics of MPCs, we reported on the identification of unique cell surface proteins which were detected with monoclonal antibodies. In this study, the phenotypic characterization of human marrow-derived MPCs is further established through the identification of a cytokine expression profile under standardized growth medium conditions and in the presence of regulators of the osteogenic and stromal cell lineages, dexamethasone and interleukin-1α (IL-1α), respectively. Constitutively expressed cytokines in this growth phase include G-CSF, SCF, LIF, M-CSF, IL-6, and IL-11, while GM-CSF, IL-3, TGF-β2, and OSM were not detected in the growth medium. Exposure of cells in growth medium to dexamethasone resulted in a decrease in the expression of LIF, IL-6, and IL-11. These cytokines have been reported to exert influence on the differentiation of cells derived from the bone marrow stroma through target cell receptors that utilize gp130-associated signal transduction pathways. Dexamethasone had no effect on the other cytokines expressed under growth medium conditions and was not observed to increase the expression of any of the cytokines measured in this study. In contrast, IL-1α increased the expression of G-CSF, M-CSF, LIF, IL-6, and IL-11 and induced the expression of GM-CSF. IL-1α had no effect on SCF expression and was not observed to decrease the production of any of the cytokines assayed. These data indicate that MPCs exhibit a distinct cytokine expression profile. We interpret this cytokine profile to suggest that MPCs serve specific supportive functions in the microenvironment of bone marrow. MPCs provide inductive and regulatory information which are consistent with the ability to support hematopoiesis, and also supply autocrine, paracrine, and juxtacrine factors that influence the cells of the marrow microenvironment itself. In addition, the cytokine profiles expressed by MPCs, in response to dexamethasone and IL-1α, identify specific cytokines whose levels of expression change as MPCs differentiate or modulate their phenotype during osteogenic or stromagenic lineage entrance/progression. © 1996 Wiley-Liss, Inc. 相似文献
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The aim of this study was to investigate the promotion of myelopoiesis by an active polysaccharide of black soybean (PSBS). Murine spleen cells were collected from ICR mice and conditioned media (SCM) was prepared by incubating these cells without PSBS (normal-SCM) or with PSBS in concentrations ranging from 12.5 to 100 microg/ml (PSBS-SCM). Murine bone marrow cells were treated with PSBS alone or SCM to induce the formation of colonies, including CFU-GM, CFU-GEMM, BFU-E and HPP-CFC. The concentrations of six hematopoietic growth factors contained in SCM were measured using enzyme-linked immunoassay. In the live animal experiment, PSBS was administered orally to total body-irradiated (TBI) and 5-fluorouracil (5-FU)-treated mice to assess the reconstitution of bone marrow after myelosuppression. PSBS-SCM stimulated CFU-GM, CFU-GEMM, BFU-E and HPP-CFC colony formation with 45.0, 5.0, 6.2 and 6.6-fold increases, respectively. However, neither PSBS alone nor normal-SCM had such a colony-stimulating effect. In PSBS-SCM, the levels of IL-6, IL-17, G-CSF and GM-CSF were markedly increased, but not those of IL-3 and SCF. Oral administration of PSBS in mice not only restored the leukocyte counts reduced by TBI and 5-FU treatment but also enhanced CFU-GM colony formation of bone marrow cells without a significant change in body weight. We conclude that PSBS promotes myelopoiesis activity in the bone marrow, stimulates production of various hematopoietic growth factors from spleen cells, and reconstitutes bone marrow that has been myelosuppressed by irradiation and 5-FU. 相似文献
17.
Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells 总被引:49,自引:0,他引:49
Multipotential bone marrow stromal cells have the ability to differentiate along multiple connective tissue lineages including cartilage. In this study, we developed an efficient and reproducible procedure for the isolation of stromal cells from bone marrow aspirates of normal human donors based on the expression of endoglin, a type III receptor of the transforming growth factor-beta (TGF-beta) receptor family. We demonstrate that these cells have the ability of multiple lineage differentiation. Stromal cells represented 2-3% of the total mononuclear cells of the marrow. The cells displayed a fibroblastic colony formation in monolayer culture and maintained similar morphology with passage. Expression of cell surface molecules by flow cytometry displayed a stable phenotype with culture expansion. When cocultured with hematopoietic CD34(+) progenitor cells, stromal cells were able to maintain their ability to support hematopoiesis in vitro. Culture expanded stromal cells were placed in a 3-dimensional matrix of alginate beads and cultured in serum-free media in the presence of TGFbeta-3 for chondrogenic lineage progression. Increased expression of type II collagen messenger RNA was observed in the TGFbeta3 treated cultures. Immunohistochemistry performed on sections of alginate beads detected the presence of type II collagen protein. This isolation procedure for stromal cells and the establishment of the alginate culture system for chondrogenic progression will contribute to the understanding of chondrogenesis and cartilage repair. 相似文献
18.
Regeneration of the intestinal epithelia: Regulation of bone marrow-derived epithelial cell differentiation towards secretory lineage cells 总被引:3,自引:0,他引:3
The intestinal epithelia consists of four lineages of differentiated cells, all of which arise from stem cells residing in the intestinal crypt. For proper regeneration from epithelial damage, both expansion of the epithelial cell number and appropriate regulation of lineage differentiation from the remaining stem cells are thought to be required. In a series of studies, we have shown that bone-marrow derived cells could promote the regeneration of damaged epithelia in the human intestinal tract. Donor-derived epithelial cells substantially repopulated the gastrointestinal tract of bone-marrow transplant recipients during epithelial regeneration after graft-versus-host disease. Furthermore, precise analysis of epithelial cell lineages revealed that during epithelial regeneration, secretory lineage epithelial cells that originated from bone-marrow significantly increased in number. These findings may lead to a novel therapy to repair damaged intestinal epithelia using bone marrow cells, and provide an alternative therapy for refractory inflammatory bowel diseases. 相似文献
19.
Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages 总被引:14,自引:0,他引:14
Hemopoietic lineage commitment can be breached by concomitant expression of the c-myc and v-raf oncogenes. Switching to the myeloid lineage occurred frequently when B lineage cells, from either lymphomas or preleukemia bone marrow cells of Emu-myc transgenic mice, were infected with a retrovirus bearing v-raf. Cloned pre-B and B cell lines changed into either mature or immature macrophages as assessed by morphology, adherence, phagocytic activity, surface markers, and lysozyme production, but retained clonotypic immunoglobulin gene rearrangements. Although expression of the Emu-myc transgene was reduced or abolished in the more differentiated lines, the lines remained tumorigenic. The converted lines produced the myeloid growth factor GM-CSF, and most had karyotypic alterations. These results suggest that constitutive myc plus raf expression can provoke genetic reprogramming in lymphocytes. 相似文献
20.
Rescue of myeloid lineage-committed preprogenitor cells from cytomegalovirus-infected bone marrow stroma. 总被引:4,自引:2,他引:2
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The effect of murine cytomegalovirus on myelopoiesis was studied in long-term bone marrow culture to find an in vitro correlate for the lethal virus interference with bone marrow reconstitution (W. Mutter, M. J. Reddehase, F. W. Busch, H.-J. Bühring, and U. H. Koszinowski, J. Exp. Med. 167:1645-1658, 1988). The in vitro generation of granulocyte-monocyte progenitors (CFU-GM) discontinued after infection of the stromal cell layer, whereas the proliferation and differentiation of CFU-GM to granulocyte-monocyte colonies remained unaffected. A protocol was established to probe the functional integrity of earlier hematopoietic cells. Pre-CFU-GM (the progenitors of the CFU-GM) could be recovered from an infected bone marrow donor culture by transfer onto an inductive recipient stromal cell layer. Thus, at least in vitro, infection of bone marrow stroma appears to be the only cause of the defect in myelopoiesis. 相似文献