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首页> 外文期刊>Infection and immunity >Enhancement of neutrophil-mediated injury to bovine pulmonary endothelial cells by Pasteurella haemolytica leukotoxin.
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Enhancement of neutrophil-mediated injury to bovine pulmonary endothelial cells by Pasteurella haemolytica leukotoxin.

机译：溶血巴斯德氏菌白细胞毒素增强嗜中性粒细胞介导的牛肺内皮细胞损伤。

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In this study, we used an in vitro coculture system to determine which virulence factor from Pasteurella haemolytica A1 was responsible for augmenting bovine polymorphonuclear neutrophil (PMN)-mediated killing of bovine pulmonary artery endothelial cells (BPAEC). A 51Cr release cytotoxicity assay was used as a measure of BPAEC killing. The mechanisms associated with this BPAEC killing were also studied. Our results demonstrated that the leukotoxin and not the lipopolysaccharide from P. haemolytica was responsible for augmenting the PMN-mediated killing of BPAEC. Furthermore, this augmented killing was related to the stimulation of PMNs by the leukotoxin. Killing of BPAEC by leukotoxin-stimulated PMNs was diminished in the presence of the H2O2 inactivator, catalase. The membrane-permeant H2O2, hydroxyl radical (HO.) scavenger 1,3-dimethyl-2 thiourea, and the HO. scavenger dimethyl sulfoxide but not the myeloperoxidase inhibitor sodium azide attenuated this BPAEC killing. Pretreatment of BPAEC with a 21-aminosteroid (U74500A), a potent iron chelator-antioxidant, provided the most effective protection against BPAEC killing induced by leukotoxin-stimulated PMNs. These data were compatible with the concept that the H2O2 generated by leukotoxin-stimulated PMNs interacts with intracellular iron in the endothelial cell to form highly reactive HO.. We suggest that HO. may be a key factor in BPAEC killing. Furthermore, since the elastase-specific inhibitor N-methoxy-succinyl-Ala-Ala-Pro-Val-chloromethyl ketone (CMK) also attenuated BPAEC killing and both CMK and 1,3-dimethyl-2 thiourea functioned additively in protecting against BPAEC killing, we conclude that both HO. and elastase may jointly contribute to BPAEC killing induced by leukotoxin-stimulated PMNs. This study broadens our understanding of how leukotoxin-stimulated PMNs injure lung endothelial cells and provides new insight into the pathogenesis of bovine pneumonic pasteurellosis.
机译：在这项研究中，我们使用了体外共培养系统来确定溶血巴斯德氏菌A1中的哪种致病因子是导致牛多形核中性粒细胞（PMN）介导的牛肺动脉内皮细胞（BPAEC）杀伤力增强的原因。使用51Cr释放细胞毒性试验作为BPAEC杀伤的量度。还研究了与此BPAEC杀死有关的机制。我们的结果表明，白细胞毒素而非溶血假单胞菌的脂多糖负责增加PMN介导的BPAEC杀伤。此外，这种增加的杀伤作用与白细胞毒素刺激PMN有关。在H2O2灭活剂过氧化氢酶的存在下，白细胞毒素刺激的PMN对BPAEC的杀伤作用降低。透过膜的H2O2，羟基自由基（HO。）清除剂1,3-二甲基-2硫脲和HO。清除剂二甲基亚砜，但不清除髓过氧化物酶抑制剂叠氮化钠，可减弱这种BPAEC杀伤力。用有效的铁螯合剂抗氧化剂21-氨基类固醇（U74500A）对BPAEC进行预处理，可以最有效地保护白细胞毒素刺激的PMN诱导的BPAEC杀伤。这些数据与白细胞毒素刺激的PMN产生的H2O2与内皮细胞中的细胞内铁相互作用形成高反应性HO的概念是一致的。可能是杀死BPAEC的关键因素。此外，由于弹性蛋白酶特异性抑制剂N-甲氧基-琥珀酰-Ala-Ala-Pro-Val-氯甲基酮（CMK）也减弱了BPAEC的杀伤力，因此CMK和1,3-二甲基-2硫脲在保护BPAEC杀伤力上具有附加作用。 ，我们得出结论两者都是HO。弹性蛋白酶可能与白细胞毒素刺激的PMN诱导的BPAEC杀伤共同起作用。这项研究拓宽了我们对白细胞毒素刺激的PMNs如何损伤肺内皮细胞的理解，并为牛肺巴氏杆菌病的发病机理提供了新的见解。

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