1997 Fiscal Year Final Research Report Summary
Mechanism of development of nasal hyperreactivity
| Project/Area Number |
07407047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Chiba University |
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Principal Investigator |
KONNO Akiyoshi Chiba University school of Medicine, Dept.of ENT,Professor, 医学部, 教授 (70009497)
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| Co-Investigator(Kenkyū-buntansha) |
NUMATA Tsutomu Chiba University school of Medicine, same as above, Lecturer, 医学部, 講師 (60189355)
HANAZAWA Toyoyuki Chiba University school of Medicine, same as above, Assistant, 医学部, 助手 (90272327)
NAGATA Hiroshi Chiba University school of Medicine, same as above, Lecturer, 医学部, 講師 (20237530)
TERADA Nibuhisa Chiba University school of Medicine, same as above, Lecturer, 医学部, 講師 (70197797)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Nasal Allergy / Nasal Hyperreactivity / Allergic Inflammation / Axon Reflex / Parasympathetic Reflex / Ehemical Mediater / Cytokine / Neurotransmitter |
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| Research Abstract |
I Mechanism of development of hyperreactive nasal symptoms in nasal allergy.
1) Nasal mucosal swelling is caused by dilatation of the cavernous sinces and plasma extravasation. Axon reflex, ganglion reflex and parasympathetic reflex participate only partially in development of nasal mucosal swelling observed in early phase after antigen challenge. The neurotransmitter which is most deeply involved in dilatation of vascular smooth muscle is NO released from parasympathetic terminals. However major partion of nasal mucosal swelling observed particularly in later phase after antigen challenge is caused by direct effects of chemical mediators on the vascular smooth muscle, the most important of which is peptide leukotriene (LTs).
2) Various mediators including LTs, histamine and bradykinin cause dilatation of vascular smooth muscle by acting on endothelial cells which release NO.
II Mechanism of nasal hyperreactivity
1) Repeated antigen challenge in subjects with pollinosis during non-pollen s
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eason caused significant increase of nasal hyperreactivity to histamine. Single antigen challenge caused significant increase of various inflammatory cells, particularly EG2 positive, activated eosinophils in the nasal lavages with concomitant increase of ECP.Antigen challenge caused significant increase of IL-5 m RNA and IL-5 in the nasal mucosa in subjects with nasal allertgy. IL-5 increased ICAM-1 m RNA in the nasal mucosa and solble ICAM-1 in nasal lavages in subjects with nasal allergy.
2) Stimulation of cultured human nasal epithelial cells and endothel caused significant production of RANTES, RANTES production was significantly enhanced in epithelial cells obtained from nasal allergy patients.
3) Stimulation of cultured human endothel by histamine in concentration above 10^<-5> M caused significant increase of eosinophil adhesion to endothelium, which was inhibitted signifiantly by premedication of anti ELAM 1 antibody.
4) Premedication of anti VLA 4 monoclonal antibody inhibitted eosinophial infiltration and LTs production observed on antigen challenge in guinea pig model of nasal allergy.
5) Expression of H1 receptor m RNA in epithelial cells was significantly enhanced in subjects with nasal allergy. Stimulation of cultured human nasal epithelial cells with beta estrogen and progesteron increased H1 recepter m RNA expression significantly. Less
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