髓源性抑制细胞对脓毒症小鼠的保护作用
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摘要
目的:研究髓源性抑制细胞(MDSCs)对脓毒症小鼠是否有保护作用。方法:采用盲肠结扎穿孔术(CLP)制作脓毒症小鼠模型,术后不同时间点检测MDSCs在脾脏中的变化。通过CLP术后腹腔注射MDSCs,观察脓毒症小鼠炎症因子及生存率的变化。结果:随着脓毒症的进展,MDSCs在脓毒症小鼠脾脏中不断聚集,可增加抗炎因子(IL-10)的产生,减少炎症因子(INF-γ)的释放,从而改善脓毒症的预后。结论:MDSCs可以减轻脓毒症的炎症反应,提高脓毒症小鼠的生存率,从而为治疗脓毒症提供新的思路。
Objective To investigate whether myeloid-derived suppressor cells(MDSCs) have a protective effect in septic mice. Methods The model of caecal ligation and puncture(CLP) was performed to induce polymicrobial sepsis in mice. The changes of MDSCs in spleens at different times after operation were studied. In order to observe the influence of MDSCs on the inflammatory factors and survival of septic mice, MDSCs were injected into the peritoneal cavities of mice after CLP. Results MDSCs accumulated in spleens of septic mice progressively. MDSCs could increase anti-inflammatory cytokine production, decrease the level of inflammatory factors, and improve the survival rate of mice with sepsis. Conclusion MDSCs can attenuate the inflammation and improve the survival rate of mice with sepsis, suggesting that intraperitoneal injection of MDSCs may provide a new direction for the treatment of sepsis.
Objective To investigate whether myeloid-derived suppressor cells(MDSCs) have a protective effect in septic mice. Methods The model of caecal ligation and puncture(CLP) was performed to induce polymicrobial sepsis in mice. The changes of MDSCs in spleens at different times after operation were studied. In order to observe the influence of MDSCs on the inflammatory factors and survival of septic mice, MDSCs were injected into the peritoneal cavities of mice after CLP. Results MDSCs accumulated in spleens of septic mice progressively. MDSCs could increase anti-inflammatory cytokine production, decrease the level of inflammatory factors, and improve the survival rate of mice with sepsis. Conclusion MDSCs can attenuate the inflammation and improve the survival rate of mice with sepsis, suggesting that intraperitoneal injection of MDSCs may provide a new direction for the treatment of sepsis.
引文
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[7]Cuenca AG,Moldawer LL.Myeloid-derived suppressor cells in sepsis:friend or foe[J]?Intensive Care Med,2012,38(6):928-930.
[8]Rittirsch D,Huber-Lang MS,Flierl MA,et al.Immunodesign of experimental sepsis by cecal ligation and puncture[J].Nat Protoc,2009,4(1):31-36.
[9]Brudecki L,Ferguson DA,McCall CE,et al.Myeloid-derived suppressor cells evolve during sepsis and can enhance or attenuate the systemic inflammatory response[J].Infect Immun,2012,80(6):2026-2034.
[10]Shubin NJ,Monaghan SF,Ayala A.Anti-inflammatory mechanisms of sepsis[J].Contrib Microbiol,2011,17:108-124.
[11]Azevedo LC.The many facets of sepsis pathophysiology and treatment[J].Shock,2013,39 Suppl 1:1-2.
[12]Delano MJ,Scumpia PO,Weinstein JS,et al.MyD88-dependent expansion of an immature GR-1(+)CD11b(+)population induces T cell suppression and Th2 polarization in sepsis[J].J Exp Med,2007,204(6):1463-1474.
[13]Sander LE,Sackett SD,Dierssen U,et al.Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function[J].J Exp Med,2010,207(7):1453-1464.
[2]Poschke I,Kiessling R.On the armament and appearances of human myeloid-derived suppressor cells[J].Clin Immunol,2012,144(3):250-268.
[3]Peranzoni E,Zilio S,Marigo I,et al.Myeloid-derived suppressor cell heterogeneity and subset definition[J].Curr Opin Immunol,2010,22(2):238-244.
[4]Cripps JG,Gorham JD.MDSC in autoimmunity[J].Int Immunopharmacol,2011,11(7):789-793.
[5]Pereira WF,Ribeiro-Gomes FL,Guillermo LV,et al.Myeloidderived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses[J].J Leukoc Biol,2011,90(6):1191-1197.
[6]Cuenca AG,Delano MJ,Kelly-Scumpia KM,et al.A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma[J].Mol Med,2011,17(3-4):281-292.
[7]Cuenca AG,Moldawer LL.Myeloid-derived suppressor cells in sepsis:friend or foe[J]?Intensive Care Med,2012,38(6):928-930.
[8]Rittirsch D,Huber-Lang MS,Flierl MA,et al.Immunodesign of experimental sepsis by cecal ligation and puncture[J].Nat Protoc,2009,4(1):31-36.
[9]Brudecki L,Ferguson DA,McCall CE,et al.Myeloid-derived suppressor cells evolve during sepsis and can enhance or attenuate the systemic inflammatory response[J].Infect Immun,2012,80(6):2026-2034.
[10]Shubin NJ,Monaghan SF,Ayala A.Anti-inflammatory mechanisms of sepsis[J].Contrib Microbiol,2011,17:108-124.
[11]Azevedo LC.The many facets of sepsis pathophysiology and treatment[J].Shock,2013,39 Suppl 1:1-2.
[12]Delano MJ,Scumpia PO,Weinstein JS,et al.MyD88-dependent expansion of an immature GR-1(+)CD11b(+)population induces T cell suppression and Th2 polarization in sepsis[J].J Exp Med,2007,204(6):1463-1474.
[13]Sander LE,Sackett SD,Dierssen U,et al.Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function[J].J Exp Med,2010,207(7):1453-1464.