Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammation
Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammation
复制标题
DOI：
10.1096/fj.02-1103fje
复制
发表时间：
2003-10-01
期刊：
影响因子：
4.8
通讯作者：
Gasque, P
中科院分区：
文献类型：
--
作者：
Francis, K;Lewis, BM;Gasque, P
内分泌系统和免疫系统之间存在使用激素和细胞因子等分子的双向通讯。在这里，我们描述了一种新的途径，C3a（一种补体衍生的细胞因子）刺激垂体前叶激素释放并激活下丘脑-垂体-肾上腺轴，这是应激反应和炎症控制的核心反射。我们发现 C3a 受体在垂体激素分泌和非激素分泌（滤泡）细胞中表达，并且 C3a 和 C3adesArg（一种非炎症代谢物）刺激垂体细胞培养物释放催乳素、生长激素和促肾上腺皮质激素。这些激素与肾上腺皮质酮的血清水平随着体内重组 C3a 和 C3adesArg 的给药而呈剂量依赖性增加。百日咳毒素会阻断对 C3a 的反应，但不会阻断对 C3adesArg 的反应，这表明存在两种受体，其中只有一种与 G(alphai) 蛋白偶联。我们提出补体先天免疫分子（细胞因子）通过与内分泌垂体的通讯来调节组织特异性和全身炎症反应。
Two-way communication exists between the endocrine and immune systems using molecules such as hormones and cytokines. Here we describe a new pathway by which C3a, a complement-derived cytokine, stimulates anterior pituitary hormone release and activates the hypothalamic-pituitary-adrenal axis, a reflex central to the stress response and to the control of inflammation. We show that C3a receptors are expressed in pituitary hormone secreting and non-hormone secreting (folliculostellate) cells and that both C3a and C3adesArg (a non-inflammatory metabolite) stimulate pituitary cell cultures to release prolactin, growth hormone, and adrenocorticotropin. Serum levels of these hormones, together with adrenal corticosterone, increase dose dependently with recombinant C3a and C3adesArg administration in vivo. Pertussis toxin blocks the response to C3a but not C3adesArg, which indicates the presence of two receptors, only one of which is coupled to G(alphai)-proteins. We propose that the complement innate immune molecules (cytokines) modulate tissue-specific and systemic inflammatory responses through communication with the endocrine pituitary gland.