1998 Fiscal Year Final Research Report Summary
Inhaled Nitric Oxide Reduces Tyrosine Nitration after LPS Instillation into Lungs of Rats
| Project/Area Number |
09470148
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
TOMITA Tomoyuki Kitasato Univ., School of Medicine, Professor, 医学部, 教授 (40050439)
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| Co-Investigator(Kenkyū-buntansha) |
IMASAKI Takao Kitasato Univ., School of Medicine, Research Associate, 医学部, 助手 (90265588)
MITSUFUJI Hisashi Kitasato Univ., School of Medicine, Research Associate, 医学部, 助手 (40260856)
KOBAYASHI Hirosuke Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (70153632)
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| Project Period (FY) |
1997 – 1998
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| Keywords | nitric oxide / ARDS / peroxynitrite / nitrotyrosine / aminotyrosine / myeloperoxidase |
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| Research Abstract |
Nitric oxide (NO) may either protect against or contribute to inflammatory lung injury. In this study we investigated whether inhalation of 20 ppm NO alters tyrosine nitration, and we assessed the degree of lung infianimation and edema in rats after lipopolysaccharide (LPS) instillation. The amount of nitrotyrosine relative to the total amount of tyrosine was measured in lung homogenates, and lung tissue sections were stained for nitrotyrosine and aminotyrosine (a reduced form of nitrotyrosine). Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, and myeloperoxidase activity was measured in lung homogenate. Lung edema and inflammatory cell accumulation in lung tissue were estimated by extravascular lung water weight (EVLW) and extravascular dry lung weight (EVDW), respectively. LPS instillation caused increases in nitrotyrosine concentration and imniunohistochemical staining of nitrotyrosine and aminotyrosine in the lungs. LPS instillation increased the BALF leukocyte count, myeloperoxidase activity in lung tissue, and both EVLW and EVDW.Inhalational exposure to 20 ppm NO induced nitrotyrosine and aminotyrosine formation only in bronchial epithelial cell surface of the lungs not instilled with LPS.NO inhalation reduced the increases in nitrotyrosine and aminotyrosine in LPS-instilled lung tissue as well as the leukocyte count in BALF and myeloperoxidase activity in lung tissue, but it did not significantly change EVLW or EVDW.Leukocyte depletion in LPS-instilled rats reduced interstitial inflammatory cells, which were stained with nitrotyrosine and aminotyrosine, and attenuated the nitrotyrosine staining of alveolar capillaries. These results suggest that inhalation of 20 ppm NO reduces leukocyte accumulation in the lungs and inhibits tyrosine nitration caused by LPS instillation.
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