PERTUSSIS ADENYLATE CYCLASE: EFFECTS ON BLOOD CELLS

百日咳腺苷酸环化酶：对血细胞的影响

• 批准号: 3081682
• 负责人: DENNIS L CONFER
• 金额: $ 6.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081682
• 关键词: Bordetella pertussis; adenylate cyclase; alveolar macrophages; bacterial cytopathogenic effect; bactericidal immunity; blood cells; cyclic AMP; exotoxins; hemolysis; host organism interaction; human tissue; inflammation; lymphocyte; neutrophil; pertussis; platelets

All successful pathogens have evolved strategies which allow survival and replication within the potentially hostile environment of the host. In many cases, these strategies are aimed at avoidance of destruction by host phagocytes. This application concerns a unique device employed by Bordetella spp. for paralyzing phagocytic cells. B. petussis (and other species of Bordetella) elaborates a soluble and higly active adenylate cyclase. We have found that this enzyme, as a result of internalization, will cause intact mammalian cells to accumulate large quantities of cyclic AMP. The cyclic AMP, in turn, disarms phagocyte bacteriocidal processes. This unusual phagocyte avoidance strategy may explain several of the peculiar characteristics of Bordetella infections, including the lack of activated oxygen production by alveolar macrophages derived from Bordetella-infected animals and the greatly enhanced susceptibility of Bordetella infected humans to secondary infections. The Research proposed in this application is aimed at further elucidation of the cellular effects of Bordetella-induced elevations of host cell cyclic AMP levels. We shall also explore the possibility that B. pertussis adenylate cyclase might be used in the purposeful modulation of a variety of cellular functions. The results of these studies should help elucidate the pathogenesis of B. pertussis infection and may provide a very useful tool for the artificial manipulation of cellular cyclic AMP concentrations. In view of the great number of drugs which act through modulation of cyclic AMP metabolism, the use of this bacterial enzyme may represent a novel and potentially powerful mode of pharmacologic manipulation of many cellular functions.

所有成功的病原体都进化出了能够生存和生存的策略 在主机的潜在敌对环境中进行复制。 在 在许多情况下，这些战略旨在避免东道国的破坏 吞噬细胞。 该申请涉及一种独特的设备，由 博德特氏菌属用于麻痹吞噬细胞。 B. petussis（以及其他 博德特氏菌 (Bordetella) 种）精心制作出一种可溶且高活性的腺苷酸 环化酶。 我们发现这种酶由于内化作用， 会导致完整的哺乳动物细胞积累大量的循环 AMP。 环磷酸腺苷反过来又解除吞噬细胞的杀菌过程。 这种不寻常的吞噬细胞回避策略可以解释其中的几个原因 博德特氏菌感染的独特特征，包括缺乏 肺泡巨噬细胞产生活性氧 感染博德特氏菌的动物及其易感性大大增强 博德特氏菌感染人类造成继发感染。 研究建议 本申请旨在进一步阐明细胞效应 博德特氏菌诱导的宿主细胞环磷酸腺苷水平升高。 我们将 还探讨了百日咳博德特氏菌腺苷酸环化酶可能是 用于有目的地调节多种细胞功能。 这 这些研究结果应有助于阐明 B. 百日咳感染并可能为人工感染提供非常有用的工具 细胞环AMP浓度的操纵。 鉴于伟大 通过调节环磷酸腺苷代谢发挥作用的药物数量， 这种细菌酶的使用可能代表一种新颖且潜在强大的 许多细胞功能的药理操作模式。

项目成果

Cell-autonomous role of endothelial GTP cyclohydrolase 1 and tetrahydrobiopterin in blood pressure regulation.

• DOI: 10.1161/hypertensionaha.114.03089
• 发表时间: 2014-09
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Chuaiphichai S;McNeill E;Douglas G;Crabtree MJ;Bendall JK;Hale AB;Alp NJ;Channon KM
• 通讯作者: Channon KM

Compressed sensing to accelerate magnetic resonance spectroscopic imaging: evaluation and application to 23Na-imaging of mouse hearts.

• DOI: 10.1186/s12968-015-0149-6
• 发表时间: 2015-06-15
• 期刊: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
• 作者: Maguire ML;Geethanath S;Lygate CA;Kodibagkar VD;Schneider JE
• 通讯作者: Schneider JE

Bordetella adenylate cyclase: host toxicity and diagnostic utility.

博德特氏菌腺苷酸环化酶：宿主毒性和诊断用途。

• 发表时间: 1985
• 期刊: Developments in biological standardization
• 作者: Confer,DL;Eaton,JW
• 通讯作者: Eaton,JW

Rapid transcriptional down-regulation of c-myc expression during cyclic adenosine monophosphate-promoted differentiation of leukemic cells.

在环磷酸腺苷促进白血病细胞分化过程中，c-myc 表达快速转录下调。

• DOI: 10.1172/jci112987
• 发表时间: 1987
• 期刊: The Journal of clinical investigation
• 作者: Slungaard,A;Confer,DL;Schubach,WH
• 通讯作者: Schubach,WH