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

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gunma University
• Principal Investigator: MORIKAWA Akihiro Gunma University Graduate School, Pediatrics & Developmental Medicine, Professor, 医学部, 教授 (40125878)
• Co-Investigator(Kenkyū-buntansha): MOCHIZUKI Hiroyuki Gunma University, Medicine, Lecturer, 医学部, 講師 (50270856)
• Project Period (FY): 2002 – 2003
• Keywords: RSV / eosinophil / oxygen radical / degranulation / airway epithelium / bronchial asthma / airway inflammation / Mac-1

Research Abstract

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.

Research Products

• [Publications] Kimura H, Kato M 他: "Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human neutrophils."Cell Biol Int. 27. 913-919 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tachibana A, Kato M 他: "Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions."Clin Exp Immunol. 130. 415-423 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki M, Kato M 他: "Inhibition of human eosinophil activation by a cysteinyl leukotriene receptor antagonist (pranlukast ; ONO-1078)."J Asthma. 40. 395-404 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 加藤政彦: "ヒト好酸球活性化の細胞内シグナル伝達機構の解明とその制御"小児アレルギー学会雑誌. 17. 163-172 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato M, Kimura H 他: "Platelet-activating factor activates two distinct effector pathways in human eosinophils"J Immunol. 169. 5252-5259 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kimura H, Kato M, Ikeda M, Nagai A, Okada Y, Naito S, Oshima S, Taniguchi K, Kozawa K, Morikawa A.: "Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human neutrophils."Cell Biol Int.. 27. 913-919 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tachibana A, Kato M, Kimura H, Fujiu T, Suzuki M, Morikawa A.: "Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions."Clin Exp Immunol.. 130. 415-423 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takizawa T, Kato M, Suzuki M, Tachibana A, Motegi Y, Fujiu T, Kimura H, Arakawa H, Mochizuki H, Tokuyama K, Morikawa A.: "Distinct isoforms of protein kinase C are involved in human eosinophil functions induced by platelet-activating factor."Int Arch Allergy Immunol.. 131 Suppl 1. 15-19 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki M, Kato M, Kimura H, Fujiu T, Morikawa A.: "Inhibition of human eosinophil activation by a cysteinyl leukotriene receptor antagonist (pranlukast; ONO-1078)."J Asthma.. 40. 395-404 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M, Minakami H, Kuroiwa M, Kobayashi Y, Oshima S, Kozawa K, Morikawa A, Kimura H.: "Superoxide radical generation and Mn-and Cu-Zn superoxide dismutases activities in human leukemic cells."Hematol Oncol.. 21. 11-16 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M, Kimura H, Motegi Y, Tachibana A, Minakami H, Morikawa A, Kita H.: "Platelet-activating factor activates two distinct effector pathways in human eosinophils."J Immunol.. 169. 5252-5259 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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. 43-45 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato M, Tokuyama K, Minakami H, Nagai A, Kozawa K, Goto H, Morikawa A, Kimura H.: "Increased superoxide radicals generation from alveolar macrophages in immature guinea-pigs."Cell Biol Int.. 26. 829-832 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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 Immunol.. 110. 241-248 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujiu T, Kato M, Kimura H, Tachibana A, Suzuki M, Nako Y, Morikawa A.: "Cellular adhesion is required for effector functions of human eosinophils via G-protein coupled receptors."Ann Allergy Asthma Immunol.. 89. 90-98 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mirza ZN, Kato M, Kimura H, Tachibana A, Fujiu T, Suzuki M, Mochizuki H, Tokuyama K, Morikawa A.: "Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms."Ann Allergy Asthma Immunol.. 88. 494-500 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より