Immune cell-derived beta-endorphin - Production, release, and control of inflammatory pain in rats
Immune cell-derived beta-endorphin - Production, release, and control of inflammatory pain in rats
复制标题
DOI：
10.1172/jci119506
复制
发表时间：
1997-07-01
影响因子：
15.9
通讯作者：
Stein, C
中科院分区：
文献类型：
--
作者：
Cabot, PJ;Carter, L;Stein, C
本文研究了淋巴细胞衍生END的产生、释放和抗伤害性效应与细胞转运的关系。在正常动物中，END和前阿片黑素皮质素在循环淋巴细胞中的含量低于在淋巴结(LN)中的含量，提示有限的细胞群产生END和LN的归宿，炎症增加了非炎症和炎症LN细胞中的前阿片黑素皮质素mRNA，而END含量仅在炎症的爪子组织和非炎症的LN免疫细胞中增加。促肾上腺皮质激素释放因子和IL-1β从非炎症的LN免疫细胞中释放的END明显多于炎症LN-免疫细胞，这种分泌是受体特异性的，依赖于钙，并被钾模仿，与囊泡释放一致。最后，这两种药物注射到炎症的爪子内，诱导的镇痛作用被抗END的抗血清共同阻断，这些发现提示，产生END的淋巴细胞聚集在炎症组织中，在那里它们分泌END以减轻疼痛，然后它们迁移到局部LN，耗尽肽，与这一概念一致，细胞悬液的免疫荧光研究表明END主要包含在记忆型T细胞中，因此，免疫系统对控制炎症性疼痛很重要，这对理解免疫抑制条件下的疼痛，如癌症或艾滋病具有重要意义。
Localized inflammation of a rat's hindpaw elicits an accumulation of beta-endorphin-(END) containing immune cells, We investigated the production, release, and antinociceptive effects of lymphocyte-derived END in relation to cell trafficking, In normal animals, END and proopiomelanocortin mRNA were less abundant in circulating lymphocytes than in those residing in lymph nodes (LN), suggesting that a finite cell population produces END and homes to LN, Inflammation increased proopiomelanocortin mRNA in cells from noninflamed and inflamed LN, However, END content was increased only in inflamed paw tissue and noninflamed LN-immune cells, Accordingly, corticotropin-releasing factor and IL-1 beta released significantly more END from noninflamed than from inflamed LN-immune cells, This secretion was receptor specific, calcium dependent, and mimicked by potassium, consistent with vesicular release, Finally, both agents, injected into the inflamed paw, induced analgesia which was blocked by the co-administration of antiserum against END, Together, these findings suggest that END-producing lymphocytes home to inflamed tissue where they secrete END to reduce pain, afterwards they migrate to the regional LN, depleted of the peptide, Consistent with this notion, immunofluorescence studies of cell suspensions revealed that END is contained predominantly within memory-type T cells, Thus, the immune system is important for the control of inflammatory pain, This has implications for the understanding of pain in immunosuppressed conditions like cancer or AIDS.