Mechanisms of exacerbation of asthma induced by RS virus infection and it's regulation due to drugs

RS病毒感染诱发哮喘发作的机制及药物调节

• 批准号: 14570723
• 负责人: MORIKAWA Akihiro
• 金额: $ 1.98万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570723/
• 关键词: RSV; eosinophil; oxygen radical; degranulation; airway epithelium; bronchial asthma; airway inflammation; Mac-1; RSウイルス; 細胞接着; スーパーオキサイド(O_2^-)産生

Human respiratory syncytial virus (RSV) infection in infancy and early childhood causes acute bronchiolitis and exacerbates bronchial asthma. Eosinophil infiltration may contribute to airway obstruction in RSV infection. We hypothesized that RSV affects eosinophil function. Eosinophil activation was evaluated by chemiluminescent detection of superoxide anion (O(2)(-)) generation. Expression of CD11b on eosinophils was determined by flow cytometry. Although RSV did not induce O(2)(-) generation by resting eosinophils, RSV enhanced O(2)(-) generation of eosinophils primed with platelet-activating factor (PAF). Enhancement was significantly inhibited by either continuous agitation to prevent eosinophil adhesion to test tube surfaces or by pretreating cells with anti-CD18 antibody, suggesting that the stimulatory effects of RSV on eosinophils depend on cell adhesion via beta(2)-integrins. In fact, RSV enhanced PAF-induced CD11b expression by eosinophils. These findings suggest that RSV enhances eosinophil CD11b expression and O(2)(-) generation induced by PAF. Thus, RSV infection may exacerbate airway inflammation by enhancing mediator release from eosinophils.

人类呼吸道合胞病毒（RSV）感染在婴儿和幼儿期引起急性细支气管炎和加重支气管哮喘。嗜酸性粒细胞浸润可能有助于呼吸道合胞病毒感染的气道阻塞。我们假设RSV影响嗜酸性粒细胞功能。通过荧光检测超氧阴离子（O（2）（-））的产生来评价嗜酸性粒细胞活化。用流式细胞术检测嗜酸性粒细胞表面CD 11b的表达。尽管RSV不诱导静息嗜酸性粒细胞产生O（2）（-），但RSV可增强血小板活化因子（PAF）引发的嗜酸性粒细胞产生O（2）（-）。通过持续搅拌以防止嗜酸性粒细胞粘附到试管表面或通过用抗CD 18抗体预处理细胞，增强被显著抑制，表明RSV对嗜酸性粒细胞的刺激作用依赖于通过β 2-整合素的细胞粘附。事实上，RSV增强PAF诱导的嗜酸性粒细胞CD 11b表达。这些结果表明，RSV增强PAF诱导的嗜酸性粒细胞CD 11b表达和O（2）（-）生成。因此，RSV感染可能通过增强嗜酸性粒细胞释放介质而加重气道炎症。

项目成果

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Kato M、Tokuyama K、Minakami H、Nagai A、Kozawa K、Goto H、Morikawa A、Kimura H.：“未成熟豚鼠肺泡巨噬细胞产生的超氧自由基增加”Cell Biol Int。

Tachibana A, Kimura H, Kato M, Nako Y, Kozawa K, Morikawa A.: "Respiratory syncytial virus enhances the expression of CD11b molecules and the generation of superoxide anion by human eosinophils primed with platelet-activating factor."Intervirology.. 45. 4

Tachibana A、Kimura H、Kato M、Nako Y、Kozawa K、Morikawa A.：“呼吸道合胞病毒增强 CD11b 分子的表达以及用血小板激活因子引发的人嗜酸性粒细胞产生超氧阴离子。”Intervirology.. 45

Takizawa T, Kato M, Kimura H, Suzuki M, Tachibana A, Obinata H, Izumi T, Tokuyama K, Morikawa A.: "Inhibition of protein kinases A and C demonstrates dual modes of response in human eosinophils stimulated with platelet-activating factor."J Allergy Clin Im

Takizawa T、Kato M、Kimura H、Suzuki M、Tachibana A、Obinata H、Izumi T、Tokuyama K、Morikawa A.：“蛋白激酶 A 和 C 的抑制表明血小板激活因子刺激的人嗜酸性粒细胞有双重反应模式

Kato M, Kita H, Tachibana A, Hayashi Y, Tsuchida Y, Kimura H.: "Dual signaling and effector pathways mediate human eosinophil activation by platelet-activating factor."Int Arch Allergy Immunol.. 134 Suppl 1. 37-43 (2004)

Kato M、Kita H、Tachibana A、Hayashi Y、Tsuchida Y、Kimura H.：“双重信号传导和效应器途径通过血小板激活因子介导人嗜酸性粒细胞活化。”Int Arch Allergy Immunol.. 134 Suppl 1. 37-43（

Takizawa T, Kato M 他: "Distinct isoforms of protein kinase C are involved in human eosinophil functions induced by platelet-activating factor."Int Arch Allergy Immunol. 131. 15-19 (2003)

Takizawa T、Kato M 等人：“蛋白激酶 C 的不同同种型参与血小板激活因子诱导的人嗜酸性粒细胞功能。”Int Arch Allergy Immunol. 131. 15-19 (2003)