Hsueh W, Sun X, Rioja L N, Gonzalez-Crussi F
Department of Pathology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614.
Immunology. 1990 Jul;70(3):309-14.
It has previously been shown that tumour necrosis factor-alpha (TNF), together with bacterial lipopolysaccharide (LPS), induces shock and bowel necrosis in the rat. Since the complement system plays an important role in inflammation and tissue injury, its role has been studied in a similar model in mice. In most of the present experiments, a low dose (0.2 micrograms/g) of TNF was used for priming, followed 30 min later by LPS (3 micrograms/g), and the experiment was terminated in 150 min. It is shown that: (i) TNF exerts no systemic effects by itself; LPS elicits only mild hypotension but causes no lethality; (ii) TNF-primed mice show exaggerated effects of shock, hypothermia, haemoconcentration and bowel injury after LPS; the majority of these mice died within 150 min; (iii) administration of LPS alone mildly activates the complement system in vivo, while TNF alone has no effect; (iv) the effects of TNF and LPS on complement activation are synergistic; (v) the acute development of shock and bowel injury in response to TNF-LPS is dependent on an intact complement system, more specifically C5, since C5-deficient mice were protected from TNF-LPS-induced shock and tissue injury; C5-deficient mice also showed less hypotension, hypothermia, haemoconcentration and better intestinal perfusion compared with C5-sufficient animals; (vi) however, when the priming dose of TNF was raised to 0.5 micrograms/g, most of the C5-deficient mice developed marked hypothermia, hypotension, haemoconcentration, bowel injury and died. Thus, it is concluded that TNF and LPS act synergistically in activating the complement system, which plays an important role in mediating the tissue injury and lethality induced by these agents.
先前的研究表明，肿瘤坏死因子-α（TNF）与细菌脂多糖（LPS）共同作用可诱导大鼠发生休克和肠坏死。由于补体系统在炎症和组织损伤中起重要作用，因此在小鼠的类似模型中对其作用进行了研究。在大多数当前实验中，使用低剂量（0.2微克/克）的TNF进行预处理，30分钟后再给予LPS（3微克/克），实验在150分钟后终止。结果表明：（i）TNF本身不产生全身效应；LPS仅引起轻度低血压，但不导致死亡；（ii）经TNF预处理的小鼠在给予LPS后表现出更严重的休克、体温过低、血液浓缩和肠损伤效应；这些小鼠中的大多数在150分钟内死亡；（iii）单独给予LPS可在体内轻度激活补体系统，而单独给予TNF则无作用；（iv）TNF和LPS对补体激活的作用具有协同性；（v）TNF-LPS诱导的休克和肠损伤的急性发展依赖于完整的补体系统，更具体地说是C5，因为C5缺陷小鼠可免受TNF-LPS诱导的休克和组织损伤；与C5充足的动物相比，C5缺陷小鼠还表现出更低的低血压、体温过低、血液浓缩以及更好的肠道灌注；（vi）然而，当TNF的预处理剂量提高到0.5微克/克时，大多数C5缺陷小鼠出现明显的体温过低、低血压、血液浓缩、肠损伤并死亡。因此，得出结论，TNF和LPS在激活补体系统方面具有协同作用，补体系统在介导这些因子诱导的组织损伤和致死性中起重要作用。
