2001 Fiscal Year Final Research Report Summary
Functional priming of inflammatory cells and modulation of their apoptosis: significance of these events in children's diseases
| Project/Area Number |
12670738
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
YASUI Kozo Shinshu University, School of Medicine, Associate Professor, 医学部・小児科, 助教授 (90200493)
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| Co-Investigator(Kenkyū-buntansha) |
AGEMATSU Kazunaga Shinshu University, School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (60262721)
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| Project Period (FY) |
2000 – 2001
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| Keywords | neutrophils / inflammation / signal transduction / monocytes / apoptosis / bronchial asthma / theophylline |
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| Research Abstract |
The unnecessary prolongation of granulocyte life and augmentation of bactericidal ability may produce toxic substances such as leukotrienes and superoxide. Activation of neutrophils ( PMN ) play key roles in systemic inflammation such as that associated with sepsis and ischemia-reperfusion injury. The regulation of cellular apoptosis and the release of toxic substances has been proposed as a key mechanism for the inhibition of inflammatory disease and tissue damage. For example, persistent inflammation in the airways is thought to be an essential feature of bronchial asthma. Histological and bronchoalveolar lavage ( BAL ) fluid studies have demonstrated that inflammatory cell infiltration exists in the airway even in cases of mild asthma, and that this cell population increases in number during severe attacks. It is well-known that neutrophils are frequently more dominant than eosinophils as the major inflammatory cells in sputa from asthmatic patients during acute exacerbation and from those with sudden onset fatal asthma attack. The presence of neutrophil elastase ( NE ) in fluids in the epithelial lining of the airway has been reported to induce further inflammatory cytokine release ( IL-8, GM CSF ) and destroy structures of the extracellular matrix ( ECM ). NE is quickly inactivated by inter- α -trypsin inhibitor ( α_2 macroglobulin ) in vivo. During this process, inter- α -trypsin inhibitor is metabolized to detectable serum trypsin inhibitor ( STI ), which could also potentially inhibit the activity of NE, thus forming a homeostatic negative feedback loop. We speculated that STI may be more dominant in patients with acute asthmatic exacerbation. Since little is known about inflammatory reactions in the airways in childhood asthma, we examined the serum levels of MMP-2, TIMP 1, NE and STI in children with acute asthma exacerbation.
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Research Products
(26 results)
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[Publications] Yasui,K., Agematsu,K, Shinozaki,K, Hokibara,S, Nagumo,H., Nakazawa,T., Komiyama,A.: "Theophylline induces neutrophilapoptosis through adenosine A ( 2A ) receptor antagonism"J Leukoc Biol. 67. 529-535 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sawai,T., Koike,K., Mwamtemi,HH. Ito,S., Kurokawa,K., Sakashita,K., Kinoshita,T., Higuchi,T., Takeuchi,K., Shiohara,M., Kamijo,T., Higuchi,Y., Miyazaki,H., Kobayashi,M., Miyake,M., Yasui,K., Komiyama,A.: "Thrombopoetin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia"J Leukoc Biol. 68. 137-143 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yasui,K., Agematsu,K., Shinozaki,K., Hokibara,S., Nagumo,H., Yamada,S., Kobayashi,N., Komiyama,A.: "Theophylline's effects on human eosin functions: comparative study with neutrophil functions"J Leukoc Biol. 68. 194-200 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Mwamtemi,HH., Koike,K., Kinoshita,T., Ito,S., Ishida,S., Nakazawa,Y., Kurokawa,Y., Shinozaki,K., Sakashita,K., Takeuchi,K., Shiohara,M., Kamijo,T., Yasui,K., Kawano,K., Miyazaki,H., Kato,T., Sakuma,S., Komiyama,A.: "An increase in circulating mast cell colony-forming cells in asthma"J Immunol. 166. 4672-4677 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nagumo,H., Agematsu,K., Kobayashi,N., Shinozaki,K., Hokibara,S., Takamoto,M., Yasui,K., Suagane,K., Komiyama,A.: "The different process of switching and somatic hypermutation; a novel analysis by CD 27 ( - ) naive B cells"Blood. 99. 567-575 (2002)
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[Publications] Shinozaki,K., Yasui,K., Agematsu,K. Nagumo,H., Naitoh,H., Naganuma, Komiyama,A.: "Familial mediterranean fever in two Japanese families"J Rheumatol. in press.
Description
「研究成果報告書概要(欧文)」より
