Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses.
Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses.
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DOI：
10.4049/jimmunol.153.12.5802
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发表时间：
1994-12
影响因子：
4.4
通讯作者：
J. Giri;J. Wells;S. Dower;C. McCall;R. Guzman;J. Slack;T. Bird;K. Shanebeck;K. Grabstein;J. Sims
中科院分区：
文献类型：
--
作者：
J. Giri;J. Wells;S. Dower;C. McCall;R. Guzman;J. Slack;T. Bird;K. Shanebeck;K. Grabstein;J. Sims
两种类型的细胞IL-1 R已被表征并从人和鼠来源克隆。II型IL-1 R具有非常短的胞质结构域，并且似乎不参与IL-1信号传导。我们证明，II型IL-1 Rs释放的中性粒细胞表面的TNF或内毒素治疗的反应。此外，脓毒症综合征患者的血清中含有升高水平的可溶性II型IL-1 R。从脓毒症患者中分离的中性粒细胞极大地增强了II型IL-1 R mRNA和细胞表面受体的表达，因此可能是血清中脱落受体的来源。在IL-1的三种形式中，可溶性II型IL-1 R以最高的亲和力结合IL-1 β，并且还选择性地抑制IL-1 β活性。我们提出，增加细胞表面表达和快速释放的预先形成的II型IL-1 R从中性粒细胞，作为一种可溶性IL-1 β结合蛋白，代表了一种机制，已演变为调节IL-1活性在败血症。
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.