Murr C, Widner B, Gerlach D, Werner-Felmayer G, Dierich M P, Wachter H, Fuchs D
Institute for Medical Chemistry and Biochemistry and Ludwig Boltzmann Institute for AIDS Research, Innsbruck, Austria.
Int Arch Allergy Immunol. 1997 Nov;114(3):224-8. doi: 10.1159/000237672.
In various cells including monocytes the cytokine interferon-gamma as well as lipopolysaccharide induce indoleamine 2,3-dioxygenase which degrades tryptophan to form L-kynurenine. We addressed the question of whether the exposure of human peripheral mononuclear cells to superantigens derived from streptococci is associated with tryptophan degradation in vitro.
Peripheral blood mononuclear cells were exposed to streptococcal erythrogenic toxins A and B and a streptococcal-derived mitogen named BX. In addition, the myelomonocytic cell line THP-1 was treated with these toxin preparations.
In peripheral blood mononuclear cells all three toxins induced tryptophan degradation. In parallel, production of interferon-gamma was found, and the tryptophan degradation could be blocked by antihuman interferon-gamma antibodies. Tryptophan degradation was not induced when the human myelocytoma cell line THP-1 was stimulated with these toxins, but there was a costimulatoty effect to interferon-gamma.
In peripheral blood mononuclear cell culture streptococcal erythrogenic toxins are able to stimulate tryptophan degradation in humans via the induction of interferon-gamma production. There seems to be no direct effect on myelomonocytic THP-1 cells. Because some of the degradation products of tryptophan, such as quinolinic acid and kynurenic acid, are toxic, superantigen-driven degradation oftryptophan may play a role for example in the development of the toxic-shock-like syndrome associated with severe group A streptococcal infections.
在包括单核细胞在内的多种细胞中，细胞因子γ干扰素以及脂多糖可诱导吲哚胺2,3-双加氧酶，该酶将色氨酸降解形成L-犬尿氨酸。我们探讨了人类外周血单个核细胞暴露于链球菌来源的超抗原是否与体外色氨酸降解有关。
将外周血单个核细胞暴露于链球菌致热外毒素A和B以及一种名为BX的链球菌来源的丝裂原。此外，用这些毒素制剂处理髓单核细胞系THP-1。
在外周血单个核细胞中，所有三种毒素均诱导色氨酸降解。同时，发现有γ干扰素产生，且色氨酸降解可被抗人γ干扰素抗体阻断。用这些毒素刺激人骨髓瘤细胞系THP-1时，未诱导色氨酸降解，但对γ干扰素存在共刺激作用。
在外周血单个核细胞培养中，链球菌致热外毒素能够通过诱导γ干扰素产生来刺激人体色氨酸降解。对髓单核细胞THP-1细胞似乎没有直接作用。由于色氨酸的一些降解产物，如喹啉酸和犬尿酸具有毒性，超抗原驱动的色氨酸降解可能在例如与A组链球菌严重感染相关的中毒性休克样综合征的发生中起作用。
