Kriegler M, Perez C, DeFay K, Albert I, Lu S D
Department of Molecular Biology, Cetus Corporation, Emeryville, California 94608.
Cell. 1988 Apr 8;53(1):45-53. doi: 10.1016/0092-8674(88)90486-2.
Tumor necrosis factor (TNF) is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia. The mechanism by which TNF induces these different disease states is unclear. We have identified and characterized a novel, rapidly inducible cell surface cytotoxic integral transmembrane form of TNF. The existence and behavior of this novel form of TNF may explain the complex physiology of this molecule. We suggest that activated monocytes synthesize transmembrane TNF at the site of inflammation and kill their targets by either cell-to-cell contact or local release of the TNF secretory component. In contrast, septic shock and cachexia may result from either acute or chronic systemic activation of monocytes, resulting in the widespread release of TNF secretory component into the circulation of the affected individual. We further suggest that cell borne cytokines and cytotoxins may be the primary mediators of directed inflammatory responses.
肿瘤坏死因子（TNF）是一种源自单核细胞的细胞毒素，与肿瘤消退、脓毒性休克和恶病质有关。TNF诱导这些不同疾病状态的机制尚不清楚。我们已经鉴定并表征了一种新型的、可快速诱导的细胞表面细胞毒性整合跨膜形式的TNF。这种新型TNF的存在和行为可能解释了该分子复杂的生理学特性。我们认为，活化的单核细胞在炎症部位合成跨膜TNF，并通过细胞间接触或TNF分泌成分的局部释放来杀死其靶标。相比之下，脓毒性休克和恶病质可能是由于单核细胞的急性或慢性全身激活，导致TNF分泌成分广泛释放到受影响个体的循环中。我们进一步认为，细胞携带的细胞因子和细胞毒素可能是定向炎症反应的主要介质。
