Bone-Larson C L, Hogaboam C M, Steinhauser M L, Oliveira S H, Lukacs N W, Strieter R M, Kunkel S L
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan. University of California, Los Angeles, California, USA.
Am J Pathol. 2000 Oct;157(4):1177-86. doi: 10.1016/S0002-9440(10)64633-0.
Mast cells participate in the host response during sepsis and have been shown to have a protective effect in a murine model of acute septic peritonitis and multi-organ failure initiated by cecal ligation and puncture (CLP). Stem cell factor (SCF) is a hematopoietic cytokine important in mast cell proliferation and activation. In the present study, we examined the protective effects of a single intraperitoneal injection of SCF given 2 hours before CLP surgery in mice. Four days after the CLP surgery, SCF pretreatment significantly improved mouse survival from 29 to 56% and mast cells were absolutely required for this effect. Immunoneutralization studies revealed that the SCF-stimulated release of monocyte chemoattractant protein-1 (MCP-1) into the septic peritoneal cavity contributed to the protective effect of SCF in this model. One potential cellular source of MCP-1 was the SCF-activated mast cell. In addition, SCF pretreatment significantly augmented circulating levels of SCF and the immunomodulatory cytokine interleukin-10 in septic mice, in part because the SCF pretreatment seemed to promote the release of both mediators from the liver. Additional hepatic effects of SCF treatment included an accelerated expression of hepatic levels of signal transducer and activator of transcription-3 (STAT-3) in CLP mice pretreated with SCF. Taken together, the findings from the present study demonstrate that the intraperitoneal delivery of SCF has a major protective effect in a murine model of CLP.
肥大细胞参与脓毒症期间的宿主反应，并且已证实在由盲肠结扎和穿刺（CLP）引发的急性脓毒症性腹膜炎和多器官功能衰竭的小鼠模型中具有保护作用。干细胞因子（SCF）是一种对肥大细胞增殖和激活很重要的造血细胞因子。在本研究中，我们检测了在CLP手术前2小时腹腔内单次注射SCF对小鼠的保护作用。CLP手术后四天，SCF预处理显著提高了小鼠存活率，从29%提高到56%，并且这种效应绝对需要肥大细胞。免疫中和研究表明，SCF刺激单核细胞趋化蛋白-1（MCP-1）释放到脓毒症腹腔中有助于SCF在该模型中的保护作用。MCP-1的一个潜在细胞来源是SCF激活的肥大细胞。此外，SCF预处理显著提高了脓毒症小鼠体内SCF和免疫调节细胞因子白细胞介素-10的循环水平，部分原因是SCF预处理似乎促进了这两种介质从肝脏的释放。SCF治疗对肝脏的其他影响包括在接受SCF预处理的CLP小鼠中加速肝脏中信号转导和转录激活因子3（STAT-3）水平的表达。综上所述，本研究结果表明腹腔内给予SCF在CLP小鼠模型中具有主要保护作用。
