Localization of S100A8 and S100A9 expressing neutrophils to spinal cord during peripheral tissue inflammation
Localization of S100A8 and S100A9 expressing neutrophils to spinal cord during peripheral tissue inflammation
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DOI：
10.1016/j.pain.2007.10.024
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发表时间：
2008-01-01
期刊：
影响因子：
7.4
通讯作者：
Iadarola, Michael J.
中科院分区：
文献类型：
--
作者：
Mitchell, Kendall;Yang, Hsiu-Ying T.;Iadarola, Michael J.
脊髓转录组水平的痛觉过敏研究表明，角叉菜胶诱导的大鼠后爪炎症导致S100A8和S100A9表达快速但持续增加，这两个基因与类风湿性关节炎和痛风等多种炎症性疾病的病理有关。原位杂交显示，在外周炎症期间，迁移到脊髓血管系统的中性粒细胞出现了升高，而不是在脊髓神经元或神经胶质细胞中。免疫组织化学分析表明，这些中性粒细胞大量释放S100A8和S100A9，但没有证明这一点。与此一致，我们检测到ICAM和VCAM的增加，这两个指标都是内皮激活的指标，这是已知的S100A8和S100A9分泌的触发因素。表达S100A8和S100A9的中性粒细胞向脊髓的迁移是有选择性的，因为在后爪炎症期间，表达MCP-1和CD68的白细胞不会增加脊髓血管中的白细胞。对脊髓中许多中性粒细胞介质的检测表明，它们的调节程度不如S100A8和S100A9。在外周炎症期间，中性粒细胞也会在脑血管和脑垂体部发生迁移。综上所述，这些发现表明，在外周组织炎症过程中，白细胞亚群与中枢神经系统之间存在相互作用，这表明S100A8和S100A9明显释放并可能通过内皮血脑屏障扩散。虽然目前的发现没有建立这些观察到的神经生理或行为与伤害性处理的相关性，但数据提出了这样一种可能性，即选择性的白细胞群体可能会将疾病或组织损伤的存在从外周传递到中枢神经系统的细胞。(C)2007年，由爱思唯尔公司代表国际疼痛研究协会出版。
Investigation of hyperalgesia at the spinal transcriptome level indicated that carrageenan-induced inflammation of rat hind paws leads to a rapid but sustained increase in S100A8 and S100A9 expression, two genes implicated in the pathology of numerous inflammatory diseases including rheumatoid arthritis and gout. In situ hybridization revealed that the elevation occurred in neutrophils that migrate to the spinal cord vasculature during peripheral inflammation, not in spinal neurons or glial cells. Immunohistochemical analysis suggests, but does not prove, that these neutrophils abundantly release S100A8 and S100A9. Consistent with this, we detected an increase in ICAM and VCAM, both indicators of endothelial activation, a known trigger for secretion of S100A8 and S100A9. Migration of S100A8- and S100A9-expressing neutrophils to spinal cord is selective, since MCP-1- and CD68-expressing leukocytes do not increase in spinal cord vasculature during hind paw inflammation. Examination of many neutrophil granule mediators in spinal cord indicated that they are not regulated to the same degree as S100A8 and S100A9. Neutrophil migration also occurs in the vasculature of brain and pituitary gland during peripheral inflammation. Together, these findings suggest an interaction between a subpopulation of leukocytes and the CNS during peripheral tissue inflammation, as implied by an apparent release and possible diffusion of S100A8 and S100A9 through the endothelial blood-brain barrier. Although the present findings do not establish the neurophysiological or behavioral relevance of these observations to nociceptive processing, the data raise the possibility that selective populations of leukocytes may communicate the presence of disease or tissue damage from the periphery to cells in the central nervous system. (c) 2007 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.