抑制SDF-1活性对MSCs上清免疫调节作用及白血病细胞HL-60增殖的影响
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摘要
目的
本实验探讨抑制基质细胞衍生因子1(SDF-1)的活性后,骨髓间充质干细胞(MSCs)培养上清对PHA刺激的异体T淋巴细胞免疫调节作用及急性髓性白血病细胞HL-60增殖的影响。
方法
应用Ficoll密度梯度离心法分离骨髓间充质干细胞,流式细胞术检测其表面标志。应用尼龙棉柱法分离异体外周血T淋巴细胞,常规培养HL-60细胞,并应用SDF-1受体CXCR4的单克隆抗体12G5阻断SDF-1的生物学效应。将MSCs上清与PHA刺激的T淋巴细胞及HL-60细胞共培养,应用MTT法检测细胞在应用单克隆抗体12G5前后增殖情况,并用ELISA法检测T淋巴细胞分泌的IL-4、IFN-γ水平。
结果
加入单克隆抗体12G5阻断SDF-1的生物学效应后,MSCs上清的促白血病细胞HL-60增殖的作用受到一定的抑制,MSCs上清抑制T淋巴细胞增殖的作用无明显的影响。T细胞单独培养组、T细胞与MSCs上清混合培养组、加入单抗12G5组培养上清测得IL-4的含量分别为8.27±2.68pg/ml、22.84±5.61pg/ml、5.35±2.51pg/ml,INF-γ的含量分别为11.75±4.95 pg/ml、165.81±14.73 pg/ml、186.99±45.09pg/ml。
结论
抑制MSCs分泌的SDF-1活性后,白血病细胞HL-60的增殖受到抑制,同时对T淋巴细胞增殖及T淋巴细胞分泌IFN-γ无明显影响,而T淋巴细胞分泌IL-4降低。
Objective
To investigate the immunoregulation of MSCs supernatant on proliferation of allogeneic T lymphocytes activated by PHA and Proliferation of Acute Myelocytic Leukemia Cell line HL-60 when the effects of SDF-1 were inhibited.
Methods
Bone marrow mesenchymal stem cells were isolated by Ficoll-Hypaque density gradient, and the surface marks were detected by flow cytometry. Allogeneic T lymphocytes from peripheral blood were harvested by nylon column and HL-60 cells were conventional cultured. SDF-1 activity was blocked with anti-CXCR4 McAb 12G5. Supernatant of MSCs was co-cultured with T lymphocytes activated by PHA and HL-60 cells. Proliferation of cells were detected by MTT. The secretion of the cytokines IL-4 and INF-γwere evaluated by ELISA.
Results
After SDF-1 activity was blocked with anti-CXCR4 McAb 12G5, the enhancement of MSCs supernatant on HL-60 cells was inhibited and the inhibition of MSCs supernatant on T lymphocytes was not obviously effected. The secretion of IL-4 were 8.27±2.68pg/ml、22.84±5.61pg/ml、5.35±2.51pg/ml and the secretion of INF-γwere 11.75±4.95 pg/ml、165.81±14.73 pg/ml、186.99±45.09pg/ml in the T-cells alone group, T-cells and MSCs supernatant co-culture group and adding McAb 12G5 group respectively.
Conclusion
Blocking SDF-1 activity can inhibit proliferation of leukemia cells and has no obvious effect on proliferation of allogeneic T Lymphocytes inhibited by MSCs supernatant and secretion of IFN-γ. The secretion of IL-4 was decreased.
本实验探讨抑制基质细胞衍生因子1(SDF-1)的活性后,骨髓间充质干细胞(MSCs)培养上清对PHA刺激的异体T淋巴细胞免疫调节作用及急性髓性白血病细胞HL-60增殖的影响。
方法
应用Ficoll密度梯度离心法分离骨髓间充质干细胞,流式细胞术检测其表面标志。应用尼龙棉柱法分离异体外周血T淋巴细胞,常规培养HL-60细胞,并应用SDF-1受体CXCR4的单克隆抗体12G5阻断SDF-1的生物学效应。将MSCs上清与PHA刺激的T淋巴细胞及HL-60细胞共培养,应用MTT法检测细胞在应用单克隆抗体12G5前后增殖情况,并用ELISA法检测T淋巴细胞分泌的IL-4、IFN-γ水平。
结果
加入单克隆抗体12G5阻断SDF-1的生物学效应后,MSCs上清的促白血病细胞HL-60增殖的作用受到一定的抑制,MSCs上清抑制T淋巴细胞增殖的作用无明显的影响。T细胞单独培养组、T细胞与MSCs上清混合培养组、加入单抗12G5组培养上清测得IL-4的含量分别为8.27±2.68pg/ml、22.84±5.61pg/ml、5.35±2.51pg/ml,INF-γ的含量分别为11.75±4.95 pg/ml、165.81±14.73 pg/ml、186.99±45.09pg/ml。
结论
抑制MSCs分泌的SDF-1活性后,白血病细胞HL-60的增殖受到抑制,同时对T淋巴细胞增殖及T淋巴细胞分泌IFN-γ无明显影响,而T淋巴细胞分泌IL-4降低。
Objective
To investigate the immunoregulation of MSCs supernatant on proliferation of allogeneic T lymphocytes activated by PHA and Proliferation of Acute Myelocytic Leukemia Cell line HL-60 when the effects of SDF-1 were inhibited.
Methods
Bone marrow mesenchymal stem cells were isolated by Ficoll-Hypaque density gradient, and the surface marks were detected by flow cytometry. Allogeneic T lymphocytes from peripheral blood were harvested by nylon column and HL-60 cells were conventional cultured. SDF-1 activity was blocked with anti-CXCR4 McAb 12G5. Supernatant of MSCs was co-cultured with T lymphocytes activated by PHA and HL-60 cells. Proliferation of cells were detected by MTT. The secretion of the cytokines IL-4 and INF-γwere evaluated by ELISA.
Results
After SDF-1 activity was blocked with anti-CXCR4 McAb 12G5, the enhancement of MSCs supernatant on HL-60 cells was inhibited and the inhibition of MSCs supernatant on T lymphocytes was not obviously effected. The secretion of IL-4 were 8.27±2.68pg/ml、22.84±5.61pg/ml、5.35±2.51pg/ml and the secretion of INF-γwere 11.75±4.95 pg/ml、165.81±14.73 pg/ml、186.99±45.09pg/ml in the T-cells alone group, T-cells and MSCs supernatant co-culture group and adding McAb 12G5 group respectively.
Conclusion
Blocking SDF-1 activity can inhibit proliferation of leukemia cells and has no obvious effect on proliferation of allogeneic T Lymphocytes inhibited by MSCs supernatant and secretion of IFN-γ. The secretion of IL-4 was decreased.
引文
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[2]Le Blanc K,Tammik L,Sundberg B,et al.Mesenchymai stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex[J].Scand J
[3]Maitar B,Szekely E,Gjini K,et al Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation Bone Marrow Transplant,2004;33:597-604
[4]Nicola M D,Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood,2002,10:285-288
[5]Meisel R,Zibert A,Laryea M,et al.Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation.Blood,2004,103:4619-4621
[6]Lee Y,Gotoh A,Kwon HJ,et al.Enhancement of intracellular signaling associated with hematopoietic cell survival in response to SDF-1/CXCL12 in synerge with other cytokines[J].Blood,2001,99(12):4307-4311.
[7]Prochazkova J,Kylarova D,Vranka P,et al.Comprative study of apoptosis detecting techniques:TUNEL,apostain,and lam in B.B iotechniques,2003;35:528-534
[8]杨文博,孔佩艳,陈幸华等。急性白血病骨髓基质细胞表达SDF-1异常。第三军医大学学报,2005;27:封2。
[9]Yasuhiro S,monzur R,Hiroaki M.Diverse Transcriptional Response of CD4~+T Cells to Stromal Cell-Derived Factor(SDF)-1:Cell Survival Promotion and Priming Effects of SDF-1 on CD4~+T Cells[J].J Immunol,2001,167(6):3064-3073
[10]Nanki T,Lipsky PE.Cutting Edge:Stromal cell-deriverd factor-1 is a co-stimulator for CD4+T cell activation[J].J Immunol,2000,164(10):5010-5014
[11]Coulomb-L'Hermin A,Amara A,Schiff C,et al.Stromal cell derived factor 1(SDF-1)and antenatal human B cell lymphopoiesis:expression of SDF-1 by mesothelial cells and biliary ductal plate epithelial cells Proc Nat Acad Sci USA,1999,96:8585-8590
[12]肖庆,曾军。SDF-1/CXCR4轴与血管新生的研究进展。国际眼科学杂志,2007;7(5):1384-1386
[13]Majumdar MK,Thiede MA,Mosca JD,et al.Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells(MSCs)and stromal cells.J Cell physiol.1998,Jul;176(1):57-66.
[14]Pittenger MF,Mackay AM,Beck SC,et al.Multineage potential of adult human mesenchymal stem cells.Science.1999 Apr2;284(5411);143-147.
[15]Service RF.Tissue engineering build new bone.Science,2000;289(12):1498.
[16]刘世清,卫爱林,陶海英等。兔骨髓基质细胞的体外培养。武汉大学学报,2003
[17]32(2)185.
[18]Gronthos S,Simmons P.J.The grgwth factor requirements of STRO-1
[19]positive human bone marrow stromal precursors under serum-deprived conditions in vitro.Blood,1995;85:929-940.
[20]司徒镇强,吴军正.细胞培养,世界图书出版社,1996:15-16
[21]Pittenger MF,Mackay AM,Beck SC,et al.Multineage potential of adult human mesenchymal stem cells.Science.1999 Apr2;284(5411);143-147.
[22]Conget PA,Minguell JJ.Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells[J].J Cell Physiol,1999,181(1):67-73.
[23]Minguell JJ,Erices A,Conget P.Mesenchymal stem cells[J].Exp Bio Med,2001,226(6):507-520
[24]Deng W,Obrocka M,fischer I,et al.In vitro differentiation of human marrow stormal stem cells into earil progenitors of neural cells by conditions that increase intracellular cyclic AMP.Biochem Biophys Res Commun,2001,282:148-152.
[25]Maniatopoulos C,Sodek J,Melcher AH.Bone formation in vitro by stromal cells obtained from bone marrow of young aduit rats.Cell Tissue Res,1988,254:317-321.
[26]Maitar B,Szekely E,Gjini K,et al Human mesenchymal stem cells support unrelated donor hematopoietic stem ceils and suppress T-cell activation Bone Marrow Transplant,2004;33:597-604
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