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首页> 外文期刊>Infection and immunity >Mitogenic Effect of Bartonella bacilliformis on Human Vascular Endothelial Cells and Involvement of GroEL
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Mitogenic Effect of Bartonella bacilliformis on Human Vascular Endothelial Cells and Involvement of GroEL

机译:芽孢杆菌对人血管内皮细胞的促成丝作用及GroEL的参与

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Bartonellae are bacterial pathogens for a wide variety of mammals. In humans, bartonellosis can result in angioproliferative lesions that are potentially life threatening to the patient, including bacillary angiomatosis, bacillary peliosis, and verruga peruana. The results of this study show that Bartonella bacilliformis, the agent of Oroya fever and verruga peruana, produces a proteinaceous mitogen for human vascular endothelial cells (HUVECs) that acts in a dose-dependent fashion in vitro with maximal activity at ≥72 h of exposure and results in a 6- to 20-fold increase in cell numbers relative to controls. The mitogen increases bromodeoxyuridine (BrdU) incorporation into HUVECs by almost twofold relative to controls. The mitogen is sensitive to heat and trypsin but is not affected by the lipopolysaccharide inhibitor polymyxin B. The mitogen does not affect caspase 3 activity in HUVECs undergoing serum starvation-induced apoptosis. The Bartonella mitogen was found in bacterial culture supernatants, the soluble cell lysate fraction, and, to a lesser degree, in insoluble cell fractions of the bacterium. In contrast, soluble cell lysate fractions from closely related B. henselae, although possessing significant mitogenicity for HUVECs, resulted in only about a twofold increase in cell numbers. Biochemical and immunological analyses identified GroEL as a participant in the observed HUVEC mitogenicity. A B. bacilliformis strain containing the intact groES-groEL operon on a multicopy plasmid was generated and used to demonstrate a correlation between HUVEC mitogenicity and GroEL levels in the lysate (r2 = 0.85). Antiserum to GroEL significantly inhibited mitogenicity of the lysate. Data also show that GroEL is located in the soluble and insoluble fractions (including inner and outer membranes) of the cell and is actively secreted by B. bacilliformis.
机译:巴尔通体是多种哺乳动物的细菌病原体。在人类中,巴尔通体病可导致可能对生命造成威胁的血管增生性病变,包括细菌性血管瘤病,细菌性乳糜泻和疣状疣膜。这项研究的结果表明,Oroya发热和百日咳秘鲁疣的病原体 Bartonella bacilliformis 产生了人类血管内皮细胞(HUVEC)的蛋白质有丝分裂原,其在体外以剂量依赖性方式发挥最大作用。暴露≥72h时,细胞活性升高,导致细胞数相对于对照增加6至20倍。有丝分裂原使掺入HUVEC中的溴脱氧尿苷(BrdU)相对于对照增加了几乎两倍。有丝分裂原对热和胰蛋白酶敏感,但不受脂多糖抑制剂多粘菌素B的影响。有丝分裂原不影响经历血清饥饿诱导的细胞凋亡的HUVEC中caspase 3的活性。在细菌培养上清液中发现了 Bartonella 有丝分裂原,在细菌的可溶细胞裂解物级分中,以及在较小程度上在细菌的不溶性细胞级分中也发现了。相反,来自密切相关的 B的可溶性细胞裂解物级分。 henselae 尽管对HUVEC具有显着的有丝分裂作用,但其细胞数量仅增加了约两倍。生化和免疫学分析确定GroEL参与了观察到的HUVEC有丝分裂性。 A B。产生了在多拷贝质粒上包含完整的 groES-groEL 操纵子的芽孢杆菌菌株,并用于证明HUVEC有丝分裂性与裂解物( r 2 = 0.85)。抗GroEL的抗血清显着抑制了裂解物的有丝分裂性。数据还显示,GroEL位于细胞的可溶和不可溶部分(包括内膜和外膜)中,并由 B主动分泌。芽孢杆菌

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