Giri J G, Wells J, Dower S K, McCall C E, Guzman R N, Slack J, Bird T A, Shanebeck K, Grabstein K H, Sims J E
Immunex Research and Development Corporation, Seattle, WA 98101.
J Immunol. 1994 Dec 15;153(12):5802-9.
Two types of cellular IL-1Rs have been characterized and cloned from both human and murine sources. The type II IL-1R has a very short cytoplasmic domain and does not seem to participate in IL-1 signaling. We demonstrate that type II IL-1Rs are released from the surface of neutrophils in response to treatment with TNF or endotoxin. In addition, serum from patients with sepsis syndrome contains elevated levels of soluble type II IL-1Rs. Neutrophils isolated from patients with sepsis have greatly enhanced expression of type II IL-1R mRNA and cell surface receptors and are therefore a likely source for the shed receptors in serum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 beta with highest affinity and also selectively inhibits IL-1 beta activity. We propose that increased cell surface expression and rapid release of preformed type II IL-1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulating IL-1 activity in sepsis.
已从人和小鼠来源鉴定并克隆出两种细胞型白细胞介素-1受体（IL-1R）。II型IL-1R的胞质结构域非常短，似乎不参与IL-1信号传导。我们证明，用肿瘤坏死因子（TNF）或内毒素处理后，II型IL-1R会从中性粒细胞表面释放出来。此外，脓毒症综合征患者的血清中可溶性II型IL-1R水平升高。从脓毒症患者分离出的中性粒细胞中，II型IL-1R信使核糖核酸（mRNA）和细胞表面受体的表达大幅增强，因此很可能是血清中脱落受体的来源。在三种形式的IL-1中，可溶性II型IL-1R与IL-1β的结合亲和力最高，并且还能选择性抑制IL-1β的活性。我们提出，中性粒细胞表面II型IL-1R表达增加并作为可溶性IL-1β结合蛋白快速释放，这代表了一种进化而来的调节脓毒症中IL-1活性的机制。
