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首页> 外文期刊>Infection and immunity >Lymphoproliferative activity of Pseudomonas exotoxin A is dependent on intracellular processing and is associated with the carboxyl-terminal portion.
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Lymphoproliferative activity of Pseudomonas exotoxin A is dependent on intracellular processing and is associated with the carboxyl-terminal portion.

机译：假单胞菌外毒素A的淋巴增生活性取决于细胞内加工，并与羧基末端部分有关。

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摘要

Pseudomonas aeruginosa exotoxin A (PE) represents a microbial superantigen that requires processing by accessory cells in order to induce the proliferation of V beta 8-bearing murine T lymphocytes. In this study, we have observed that PE requires intracellular processing by a protease in order to induce lymphoproliferation. Pepstatin A, an inhibitor of acid proteases, inhibited PE-induced lymphoproliferation, whereas leupeptin, an inhibitor of serine and thiol proteases, had no effect on PE-induced lymphoproliferation. A number of mutant forms of PE were examined for their ability to induce lymphoproliferation. The mutant form which lacks amino acids 5 to 224 of the receptor-binding domain, PE43, was capable of inducing murine thymocytes to proliferate in the presence of accessory cells. However, neither PEgly276, a mutant toxin which undergoes a different intracellular processing pattern than wild-type PE, nor PE589, a mutant toxin which lacks amino acids 590 to 613 at the carboxyl terminus, was able to induce thymocyte proliferation. In addition, the lymphoproliferation induced by the PE43 mutant form of PE could also be inhibited by pepstatin A. Therefore, our data indicate that intracellular processing by a proteolytic enzyme which is inhibited by pepstatin A is critical for PE-induced lymphoproliferation. Furthermore, the lymphoproliferative activity of PE is associated with the carboxyl-terminal portion of PE.
机译：铜绿假单胞菌外毒素A（PE）代表一种微生物超抗原，需要通过辅助细胞进行处理才能诱导带有V beta 8的鼠T淋巴细胞增殖。在这项研究中，我们已经观察到PE需要细胞内蛋白酶处理才能诱导淋巴增殖。 Pepstatin A（酸性蛋白酶的抑制剂）抑制PE诱导的淋巴增殖，而Leupeptin（丝氨酸和硫醇蛋白酶的抑制剂）对PE诱导的淋巴增殖没有影响。检查了PE的许多突变形式诱导淋巴细胞增殖的能力。缺少受体结合结构域PE43的5至224位氨基酸的突变形式，能够诱导鼠胸腺细胞在存在辅助细胞的情况下增殖。但是，PEgly276（一种与野生型PE经历不同的细胞内加工模式的突变毒素）和PE589（一种在羧基末端缺少590至613位氨基酸的突变毒素）都不能诱导胸腺细胞增殖。另外，pepstatin A也可以抑制PE43突变体形式的PE诱导的淋巴增殖。因此，我们的数据表明，被pepstatin A抑制的蛋白水解酶的细胞内加工对于PE诱导的淋巴增殖至关重要。此外，PE的淋巴增生活性与PE的羧基末端部分有关。

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