CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: a potential pathway that regulates the severity of Gram-negative infections
CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: a potential pathway that regulates the severity of Gram-negative infections
复制标题
DOI：
10.1002/jlb.63.2.245
复制
发表时间：
1998-02-01
影响因子：
5.5
通讯作者：
Evans, R
中科院分区：
文献类型：
--
作者：
Chapoval, AI;Kamdar, SJ;Evans, R
已知 CSF-1 可在体外启动单核吞噬细胞 (MNP) 进行炎症刺激。我们假设体内的 CSF-1 可以使宿主对肿瘤坏死因子 α (TNF-α) 和白细胞介素 6 (IL-6) 等内毒素休克介质的产生增加敏感。事实上，当 CSF-1 引发的小鼠受到脂多糖 (LPS) 攻击时，检测到血清 IL-6 和 TNF-α 水平升高。静脉内和腹膜内注射 CSF-1 都会导致对 LPS 攻击的敏感性增加，当通过腹膜内途径给药时，这会诱导血清 IL-6 的最大增加。对照组和 CSF-1 引发的小鼠血清 IL-6 产生峰值出现在 LPS 注射后 2-3 小时，而 TNF-α 产生峰值出现在 1-2 小时。当从注射 LPS 的 CSF-1 引发的小鼠中分离外周血白细胞、脾细胞和驻留腹膜细胞 (PC) 时，只有 PC 被证明持续释放 IL-6，而没有一个 PC 释放 TNF-α。腹腔内CSF-1引发后从各种细胞和组织中分离的mRNA的比较表明，只有PC表达IL-6 mRNA，而PC、肝脏和脾脏表达TNF-α mRNA。所有组织均表现出响应 LPS 攻击的 IL-6 和 TNF-α mRNA 水平升高。在用 LPS 攻击的 CSF-1 引发的小鼠中，只有肝脏和肾脏显示出 IL-6 表达水平增强，而肝脏、肺和肾脏则显示出 TNF-α 表达增强。这些数据表明，CSF-1 启动组织 MNP，但不启动循环 MNP 转录 mRNA 并释放 IL-6 和 TNF-α。总体而言，数据表明CSF-1在调节宿主对内毒素病理生理效应的敏感性中发挥重要作用。
CSF-1 is known to prime mononuclear phagocytes (MNP) for inflammatory stimuli in vitro. We hypothesized that CSF-1 in vivo can sensitize the host to the increased production of endotoxic shock mediators such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Indeed, when CSF-1-primed mice were challenged with lipopolysaccharide (LPS), increased levels of serum IL-6 and TNF-alpha were detected. Both intravenous and intraperitoneal injections of CSF-1 resulted in increased sensitivity to LPS challenge, which induced maximum increases in serum IL-6 when administered via the intraperitoneal route. The peak serum IL-6 production in control and CSF-1-primed mice occurred 2-3 h after LPS injection, whereas that of TNF-alpha occurred by 1-2 h. When peripheral blood leukocytes, spleen cells, and resident peritoneal cells (PC) were isolated from CSF-1-primed mice injected with LPS, only the PC were shown to release IL-6 constitutively and none released TNF-alpha. A comparison of mRNA isolated from various cells and tissues after intraperitoneal CSF-1 priming indicated that only PC expressed IL-6 mRNA, whereas PC, liver, and spleen expressed TNF-alpha mRNA. All tissues showed increased levels of IL-6 and TNF-alpha mRNA in response to LPS challenge. Only liver and kidney showed an enhanced level of IL-6 expression in CSF-1-primed mice challenged with LPS, whereas liver, lung, and kidney showed enhanced TNF-alpha expression. These data indicate that CSF-1 primes tissue MNP but not circulating MNP to transcribe mRNA and release IL-6 and TNF-alpha. Overall, the data suggest that CSF-1 plays an important role in regulating the sensitivity of the host to the pathophysiological effects of endotoxin.