Blockade of Kupffer cells prevents the febrile and preoptic prostaglandin E2 responses to intravenous lipopolysaccharide in guinea pigs.
Blockade of Kupffer cells prevents the febrile and preoptic prostaglandin E2 responses to intravenous lipopolysaccharide in guinea pigs.
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库普弗细胞的阻断可防止豚鼠的发热和视前前列腺素 E2 对静脉内脂多糖的反应。
DOI：
10.1111/j.1749-6632.1997.tb51732.x
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发表时间：
1997
影响因子：
5.2
通讯作者：
Blatteis,CM
中科院分区：
文献类型：
--
作者：
Sehic,E;Hunter,WS;Ungar,AL;Blatteis,CM
通常认为发热由外源性热原（例如，细菌内毒素脂多糖[LPSI]）激活的免疫细胞在外周诱导的内源性热原（细胞因子;例如，白细胞介素-lp [IL-lp]）介导，释放到血流中并转运到大脑。事实上，大量证据表明循环LPS被各种驻留巨噬细胞清除，特别是肝脏中的巨噬细胞（枯否细胞），并且这些细胞产生细胞因子。然而，迄今为止还没有直接证据表明枯否细胞对发热的作用至关重要。因为血脑屏障（BBB）的存在先验地排除了细胞因子自由通过进入脑，所以已经假设它们可以到达特别是终板血管器（OVLT）的血管周围空间，其中BBB是泄漏的，并结合分布在其中的受体，从而诱导将原始热原信息进一步传递到神经堆中的新信号。然而，也有人推测，或者，循环LPS本身可能与这些空间中的巨噬细胞结合，从而启动细胞因子的局部产生，然后细胞因子可以介导热原信号进一步进入大脑。事实上，巨噬细胞和分支小胶质细胞在OVLT区域1 * 2已被证明表达剂量依赖性IL-1/3 mRNA后，静脉注射LPS，然而，这一消息的出现显着滞后于发烧的发作。为了确定是否全身性LPS激活巨噬细胞主要在OVLT或在肝脏中启动发热反应，我们进行了两个实验。1)假设LPS会与这些结构中的一个或两个中的细胞结合，因此，其作用部位可能是分化的，我们注射了异硫氰酸荧光素（F1 TC）标记的E。coli LPS（SigmaChemical，St. Louis，MO; 2.5mg/kg）注射到6只大鼠的颈动脉中，15分钟后，部分由NIH赠款NS 22716和NS 34857支持。通讯作者。联系电话：(901)448-5845;传真：（901）448-7126;电子邮件：bIatteis@ physiol. utterfly。edu.
It is generally believed that fever is mediated by endogenous pyrogens (cytokines; eg, interleukin-lp [IL-lp]) induced peripherally by exogenous pyrogen (eg, bacterial endotoxic lipopolysaccharide [LPSI)-activated immune cells, released into the bloodstream, and transported to the brain. Indeed, abundant evidence indicates that circulating LPS is cleared by various resident macrophages, particularly those in the liver (Kupffer cells), and that these cells produce cytokines. There is no direct evidence to date, however, that the contribution of Kupffer cells is critical to fever production. Because the presence of a blood-brain barrier (BBB) a priori precludes the free passage of cytokines into the brain, it has been hypothesized that they may reach the perivascular spaces of, in particular, the organum vasculosum laminae terminalis (OVLT), where the BBB is leaky, and bind to receptors distributed therein, thereby inducing new signals that transmit the original pyrogenic message further into the neuropile. However, it has also been speculated that, alternatively, circulating LPS may itself bind to macrophages in these spaces, thereby initiating the local production of cytokines which then could mediate the pyrogenic signal further into the brain. Indeed, macrophages and ramified microglia1* 2 in the OVLT region have been shown to express dosedependently IL-1/3 mRNA after the intravenous (iv) injection of LPS; however, the appearance of this message lags significantly behind the onset of fever. To ascertain whether systemic LPS activates macrophages preponderantly in the OVLT or in the liver to initiate the febrile response, we conducted two experiments. 1) On the assumption that LPS would bind to cells in either or both of these structures and that, therefore, its site of action might be differentiated, we injected fluorescein isothiocyanate (F1TC)-labeled E. coli LPS (Sigma Chemical, St. Louis, MO; 2.5 mg/kg) into the carotid artery of 6 rats, and 15 min later a Supported, in part, by NIH Grants NS 22716 and NS34857. Corresponding author. Tel.:(901) 448-5845; Fax:(901) 448-7126; E-mail: bIatteis@ physiol. utmem. edu.