CONTINUOUS NITRIC-OXIDE SYNTHESIS BY INDUCIBLE NITRIC-OXIDE SYNTHASE IN NORMAL HUMAN AIRWAY EPITHELIUM IN-VIVO

被引:427
作者
GUO, FH
DERAEVE, HR
RICE, TW
STUEHR, DJ
THUNNISSEN, FBJM
ERZURUM, SC
机构
[1] CLEVELAND CLIN FDN, DEPT PULM & CRIT CARE MED, CLEVELAND, OH 44195 USA
[2] CLEVELAND CLIN FDN, DEPT CANC BIOL, CLEVELAND, OH 44195 USA
[3] CLEVELAND CLIN FDN, DEPT IMMUNOL, CLEVELAND, OH 44195 USA
[4] CLEVELAND CLIN FDN, DEPT CARDIOTHORAC SURG, CLEVELAND, OH 44195 USA
[5] UNIV LIMBURG, DEPT PATHOL, 6200 MD MAASTRICHT, NETHERLANDS
关键词
D O I
10.1073/pnas.92.17.7809
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nitric oxide (NO) is an important mediator of inflammatory responses in the lung and a key regulator of bronchomotor tone. An airway NO synthase (NOS; EC 1.14.13.39) has been proposed as a source of endogenous NO in the lung but has not been clearly defined. Through molecular cloning, we conclusively demonstrate that NO synthesis in normal human airways is due to the continuous expression of the inducible NOS (iNOS) isoform in airway epithelial cells. Although iNOS mRNA expression is abundant in airway epithelial cells, expression is not detected in other pulmonary cell types, indicating that airway epithelial cells are unique in the continuous pattern of iNOS expression in the lung. In situ analysis reveals all airway epithelial cell types express iNOS, However, removal of epithelial cells from the in vivo airway environment leads to rapid loss of oNOS expression, which suggests expression is dependent upon conditions and/or factors present in the airway. Quantitation of NOS activity in epithelial cell lysates indicates nanomolar levels of NO synthesis occur in vivo. Remarkably, the high-level iNOS expression is constant in airway epithelium of normal individuals over time. However, expression is strikingly decreased by inhaled corticosteroids and beta-adrenergic agonists, medications commonly used in treatment of inflammatory airway diseases. Based upon these findings, we propose that respiratory epithelial cells are key inflammatory cells in the airway, functioning in host defense and potentially playing a role in airway inflammation.
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页码:7809 / 7813
页数:5
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