Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha.
Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha.
复制标题
DOI：
10.4049/jimmunol.149.3.918
复制
发表时间：
1992-08
影响因子：
4.4
通讯作者：
Ingrid Görgen;T. Hartung;Marcel Leist;M. Niehörster;G. Tiegs;Stefan Uhlig;F. Weitzel;Albrecht Wendel
中科院分区：
文献类型：
--
作者：
Ingrid Görgen;T. Hartung;Marcel Leist;M. Niehörster;G. Tiegs;Stefan Uhlig;F. Weitzel;Albrecht Wendel
重组人粒细胞CSF （G-CSF）预处理对两种不同感染性休克模型小鼠的保护作用。静脉注射250微克/kg的G-CSF可防止5 mg/kg LPS致小鼠死亡。注射50微克/千克G-CSF可保护半乳糖胺致敏小鼠免受lps诱导的肝炎。在任何一种情况下，这种保护都伴随着lps诱导的血清TNF活性的抑制。相反，半乳糖胺致敏小鼠用50微克/千克的小鼠重组粒细胞/巨噬细胞CSF代替G-CSF，然后用LPS刺激，血清TNF活性显著增强，死亡率增加。G-CSF对lps诱导的TNF生成的抑制作用也在大鼠中得到证实。在体内，lps处理的大鼠经G-CSF预处理后，血液中未检测到TNF。在体外，由g - csf处理的大鼠制备的肺泡巨噬细胞、骨髓巨噬细胞、库普弗细胞或腹膜巨噬细胞在LPS刺激下产生的TNF明显低于对照大鼠的相应群体。然而，当这些巨噬细胞群与G-CSF体外孵育时，lps诱导的TNF生成不受影响。这些数据表明，G-CSF介导的TNF生成抑制不是G-CSF对巨噬细胞的直接作用。为了检验在不受LPS保护的情况下，G-CSF处理是否仍能激活中性粒细胞，研究表明，G-CSF处理大鼠的粒细胞被pma诱导的氧化破裂和离子载体/花生四烯酸刺激的脂氧合酶产物形成所激活。本研究的实验支持G-CSF是革兰氏阴性脓毒症中巨噬细胞来源的tnf - α产生的负反馈信号的观点。
Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.