Suttles J, Giri J G, Mizel S B
Department of Microbiology and Immunology, Wake Forest University Medical Center, Winston-Salem, NC 27103.
J Immunol. 1990 Jan 1;144(1):175-82.
In the present study we have demonstrated that the murine IL-1 alpha precursor lacks a cleavable signal sequence and does not undergo cotranslational translocation across microsomal membranes in vitro. Culture supernatants of the murine macrophage cell line, P388D, or from normal peritoneal macrophages collected within 0.5 to 3 h after stimulation contained the 33,000 m.w. precursor as the predominant form of IL-1 alpha. Over an 18-h period, the level of low m.w. IL-1 alpha increased as the secreted precursor was processed by extracellular and/or cell surface-associated proteolytic enzymes. The calcium ionophores A23187 and ionomycin were found to dramatically enhance the release and processing of murine and human IL-1. The rapid release of IL-1 in response to a change in the intracellular level of calcium does not appear to be caused by release of a membrane-bound form of the protein, nor is there evidence that IL-1 is packaged and released from cytoskeletal associated secretory granules. In marked contrast, calcium ionophores do not induce secretion of IL-1 from a nonmacrophage cell line that synthesizes but does not normally secrete IL-1. Our results suggest that activated macrophages possess a novel processing independent, possibly calcium-dependent, mechanism that allows for the release of the precursor forms of IL-1 alpha and IL-1 beta.
在本研究中，我们已证明小鼠IL-1α前体缺乏可裂解的信号序列，并且在体外不会跨微粒体膜进行共翻译转运。小鼠巨噬细胞系P388D或刺激后0.5至3小时内收集的正常腹腔巨噬细胞的培养上清液中，33,000分子量的前体是IL-1α的主要形式。在18小时内，随着分泌的前体被细胞外和/或细胞表面相关的蛋白水解酶加工，低分子量IL-1α的水平升高。发现钙离子载体A23187和离子霉素可显著增强小鼠和人IL-1的释放和加工。响应细胞内钙水平变化而快速释放IL-1似乎不是由膜结合形式的蛋白质释放引起的，也没有证据表明IL-1是从细胞骨架相关的分泌颗粒中包装和释放的。与之形成鲜明对比的是，钙离子载体不会诱导合成但通常不分泌IL-1的非巨噬细胞系分泌IL-1。我们的结果表明，活化的巨噬细胞具有一种新的加工独立、可能依赖钙的机制，该机制允许释放IL-1α和IL-1β的前体形式。
