INTERLEUKIN-1 IS PROCESSED AND RELEASED DURING APOPTOSIS
INTERLEUKIN-1 IS PROCESSED AND RELEASED DURING APOPTOSIS
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DOI：
10.1073/pnas.88.19.8485
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
CHAPLIN, DD
中科院分区：
文献类型：
--
作者：
HOGQUIST, KA;NETT, MA;CHAPLIN, DD
白细胞介素（IL-）1-α和1-β合成为31至34 kDa的前分子。它们从单核细胞和巨噬细胞中释放，作为蛋白水解处理的17-kDa成熟分子，以高亲和力结合靶细胞上的特异性受体。IL-1不通过经典的分泌途径释放。前分子以胞质蛋白的形式合成，不含信号肽。虽然将前分子转化为成熟形式的蛋白酶是胞质酶，但未检测到与细胞相关的加工的IL-1，而仅在培养上清液中发现。我们在这里证明，释放IL-1是有效地诱导细胞损伤。当损伤导致细胞坏死时，IL-1-α作为未加工和加工分子的混合物释放，但IL-1-β仅作为生物学上无活性的前体释放。相反，当细胞经历凋亡时，IL-1-α和IL-1-β的成熟是有效的。当细胞凋亡迅速时，如在作为同种异体特异性细胞毒性T淋巴细胞的靶的巨噬细胞中，观察到细胞内发生加工。这些发现表明，细胞损伤是释放IL-1的重要生理刺激。损伤的性质深刻地影响释放的IL-1的形式。
Interleukin (IL-) 1-alpha and 1-beta are synthesized as 31- to 34-kDa pro molecules. They are released from monocytes and macrophages as proteolytically processed 17-kDa mature molecules that bind with high affinity to specific receptors on target cells. IL-1 is not released via the classic secretory pathway. The pro molecules are synthesized as cytosolic proteins without signal peptides. Although the proteases that convert the pro molecules to the mature forms are cytosolic enzymes, processed IL-1 is not detected associated with the cell but is found only in culture supernatants. We demonstrate here that release of IL-1 is efficiently induced by cell injury. When the injury causes cellular necrosis, IL-1-alpha is released as a mixture of unprocessed and processed molecules but IL-1-beta is released exclusively as the biologically inactive pro form. In contrast, when cells undergo apoptosis, maturation of both IL-1-alpha and IL-1-beta is efficient. When apoptosis is rapid, as in macrophages that are targets for allospecific cytotoxic T lymphocytes, processing is observed to occur intracellularly. These findings suggest that cell injury is an important physiologic stimulus for release of IL-1. The nature of the injury profoundly affects the forms of IL-1 that are released.