Ghiara P, Marchetti M, Blaser M J, Tummuru M K, Cover T L, Segal E D, Tompkins L S, Rappuoli R
Immunobiological Research Institute Siena, Chiron Biocine SpA, Italy.
Infect Immun. 1995 Oct;63(10):4154-60. doi: 10.1128/iai.63.10.4154-4160.1995.
The pathogenic role of Helicobacter pylori virulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxic H. pylori strains (NCTC 11637, 60190, 84-183, and 87A300 [CagA+/Tox+]). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments with extracts from noncytotoxic strains (G21 and G50 [CagA-/Tox-]) and from strains that express either CagA alone (D931 [CagA+/Tox-]) or the cytotoxin alone (G104 [CagA-/Tox+]). The treatment with extracts from cytotoxic strains induced various epithelial lesions (vacuolation, erosions, and ulcerations), recruitment of inflammatory cells in the lamina propria, and a marked reduction of the mucin layer. Extracts of noncytotoxic strains induced mucin depletion but no other significant pathology. Crude extracts of strain D931, expressing CagA alone, caused only mild infiltration of inflammatory cells, whereas extracts of strain G104, expressing cytotoxin alone, induced extensive epithelial damage but little inflammatory reaction. Loss of the mucin layer was not associated with a cytotoxic phenotype, since this loss was observed in mice treated with crude extracts of all strains. The pathogenic roles of CagA, cytotoxin, and urease were further assessed by using extracts of mutant strains of H. pylori defective in the expression of each of these virulence factors. The results obtained suggest that (i) urease activity does not play a significant role in inducing the observed gastric damage, (ii) cytotoxin has an important role in the induction of gastric epithelial cell lesions but not in eliciting inflammation, and (iii) other components present in strains which carry the cagA gene, but distinct from CagA itself, are involved in eliciting the inflammatory response.
已利用胃病小鼠模型研究了幽门螺杆菌毒力因子的致病作用。用不同剂量的细胞毒性幽门螺杆菌菌株（NCTC 11637、60190、84 - 183和87A300 [CagA+/Tox+]）的超声提取物对BALB/c小鼠进行口服处理。评估胃黏膜组织切片的病理效应，并与用非细胞毒性菌株（G21和G50 [CagA-/Tox-]）以及单独表达CagA的菌株（D931 [CagA+/Tox-]）或单独表达细胞毒素的菌株（G104 [CagA-/Tox+]）的提取物处理后的效应进行比较。用细胞毒性菌株的提取物处理会诱导各种上皮病变（空泡形成、糜烂和溃疡）、固有层中炎症细胞的募集以及黏蛋白层的显著减少。非细胞毒性菌株的提取物会导致黏蛋白耗竭，但无其他明显病理变化。仅表达CagA的D931菌株的粗提物仅引起炎症细胞的轻度浸润，而仅表达细胞毒素的G104菌株的提取物会诱导广泛的上皮损伤，但炎症反应轻微。黏蛋白层的丧失与细胞毒性表型无关，因为在用所有菌株的粗提物处理的小鼠中均观察到这种丧失。通过使用幽门螺杆菌这些毒力因子表达缺陷的突变菌株的提取物，进一步评估了CagA、细胞毒素和脲酶的致病作用。所得结果表明：（i）脲酶活性在诱导观察到的胃损伤中不发挥重要作用；（ii）细胞毒素在诱导胃上皮细胞病变中起重要作用，但在引发炎症方面不起作用；（iii）携带cagA基因但与CagA本身不同的菌株中存在的其他成分参与引发炎症反应。
