The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations
The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations
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DOI：
10.1111/j.1750-3639.1998.tb00189.x
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发表时间：
1998-10-01
期刊：
影响因子：
6.4
通讯作者：
Rivest, S
中科院分区：
文献类型：
--
作者：
Lacroix, S;Feinstein, D;Rivest, S
全身注射细菌内毒素脂多糖（LPS）提供了一个很好的手段，增加释放促炎细胞因子的循环单核细胞和组织巨噬细胞。现在有相当多的证据表明，LPS通过细胞表面受体CD 14对单核吞噬细胞发挥作用。本研究的目的是验证假设，大脑也有能力表达编码LPS受体的基因，这可能允许在血液脓毒症期间内毒素对特定细胞群的直接作用。全身注射（静脉注射或腹腔注射）后1、3、6和24小时，将成年雄性Sprague-Bawley大鼠处死注射LPS或载体溶液。将大脑从嗅球切至髓质，取30 μ m冠状切片，用特异性S-35标记的核糖核酸探针通过原位杂交组织化学法测定编码大鼠CD 14的mRNA。结果显示，在基础条件下，软脑膜、脉络丛和脑微血管系统的沿着血管中的CD 14 mRNA水平较低。全身注射细菌内毒素导致编码CD 14的基因在这些相同的结构内以及在室周器官（CVO）终板、穹窿下器官、正中隆起和最后区的血管器中的表达显著增加。在大多数这些结构中，CD 14 mRNA的信号首先在1 h检测到，在注射后3 h达到峰值，在6 h下降，并在LPS处理后24 h恢复到基础水平。非常有趣的是，在LPS注射后3和6 h，从所有感觉CVO观察到CD 14阳性细胞的移行样模式到更深的脑实质。在6小时后的挑战，小的阳性细胞被发现在整个脑实质和双标记程序表明，不同的细胞的髓源性有能力表达CD 14在响应系统性LPS。这些包括CVO小胶质细胞，脉络丛和软脑膜巨噬细胞，实质和血管周围相关的小胶质细胞，虽然特定的非髓细胞也为LPS受体阳性。这些结果提供了LPS对中枢神经系统的特定细胞群的直接作用的第一个证据，其可能负责促炎细胞因子的转录;首先在来自血液的可接近结构内，然后在严重脓毒症期间通过分散的实质细胞。
Systemic injection of the bacterial endotoxin lipopolysaccharide (LPS) provides a very good mean for increasing the release of proinflammatory cytokines by circulating monocytes and tissue macrophages. There is now considerable evidence that LPS exerts its action on mononuclear phagocytes via the cell surface receptor CD14. The aim of the present study was to verify the hypothesis that the brain has also the ability to express the gene encoding the LPS receptor, which may allow a direct action of the endotoxin onto specific cellular populations during blood sepsis. Adult male Sprague-Bawley rats were sacrificed 1, 3, 6 and 24 h after systemic (i.v. or i.p.) injection of LPS or the vehicle solution. Brains were cut from the olfactory bulb to the medulla in 30-mu m coronal sections and mRNA encoding rat CD14 was assayed by in situ hybridization histochemistry using a specific S-35-labeled riboprobe. The results show low levels of CD14 mRNA in the leptomeninges, choroid plexus and along blood vessels of the brain microvasculature under basal conditions. Systemic injection of the bacterial endotoxin caused a profound increase in the expression of the gene encoding CD14 within these same structures as well as in the circumventricular organs (CVOs) the organum vasculosum of the lamina terminalis, subfornical organ, median eminence and area postrema. In most of these structures, the signal for CD14 mRNA was first detected at 1 h, reached a peak at 3 h post-injection, declined at 6 h, and return to basal levels 24 h after LPS treatment. Quite interestingly, a migratory-like pattern of CD14 positive cells was observed from all sensorial CVOs to deeper parenchymal brain 3 and 6 h after LPS injection. At 6 h post-challenge, small positive cells were found throughout the entire parenchymal brain and dual-labeling procedure indicated that different cells of myeloid origin have the ability to express CD14 in response to systemic LPS. These included CVO microglia, choroid plexus and leptomeninge macrophages, parenchymal and perivascular-associated microglial cells, although specific nonmyeloid cells were also positive for the LPS receptor. These results provide the very first evidence of a direct role of LPS on specific cell populations of the central nervous system, which is likely to be responsible for the transcription of proinflammatory cytokines; first within accessible structures from the blood and thereafter through scattered parenchymal cells during severe sepsis.