[Three cases of respiratory bronchiolitis-associated interstitial lung disease (RB-ILD): a study of HRCT-pathologic correlation].

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a clinicopathologic entity occurring rarely in smokers. We report three cases of RB-ILD diagnosed pathologically by surgical lung biopsy. Cough was observed in all cases, sputum in one case and dyspnea on exertion in another. Reduction of diffusing capacity was observed in all three cases. No abnormality was found in the chest radiographs of any case. However, in high-resolution computed tomography (HRCT), ground-glass opacities and centrilobular nodules were observed in all three cases, emphysema in one case, intralobular linear or reticular opacities in two cases, small subpleural cysts in two and emphysema in one. Histologic examination of lung biopsy specimens taken by thoracoscopy showed peribronchiolar fibrosis and centrilobular intraluminal accumulation of macrophages in all three cases, centrilobular emphysema, membranous bronchioles filled with mucus and macrophages, and focal microscopic honeycombing in subpleural lesions in one case each. RB-ILD should be included in the differential diagnosis of interstitial lung disease in smokers.

Alkalosis stimulates endothelial nitric oxide synthase in cultured human pulmonary arterial endothelial cells.

To investigate the effect of extracellular pH on endothelial nitric oxide synthase (eNOS) in human pulmonary arteries, we measured eNOS activity and expression as well as some ion channels in human pulmonary arterial endothelial cells (HPAEC) exposed to various pH levels (6.6-8.0). eNOS activity was found to increase with alkalization and decrease with acidification, while Ca2+ uptake into HPAEC increased with alkalization. The addition of 3',4'-dichlorobenzamil hydrochloride, an inhibitor of the Na+/Ca2+ exchanger (NCX), prevented the increase of eNOS activity with alkalosis. Exposure to alkalosis and acidosis increased eNOS and NCX mRNA levels. These results suggest that an elevation of extracellular pH activates eNOS via the influx of extracellular Ca2+ and that NCX also regulates eNOS activity during alkalosis. Furthermore, NCX may have a tight interaction with eNOS at the level of transcription and might affect pulmonary circulation during alkalosis and acidosis.

Leukotoxin-activated human pulmonary artery endothelial cell produces nitric oxide and superoxide anion.

To provide evidence that pulmonary endothelial cells exposed to 9,10-epoxy-12-octadecenoate (Lx) produce nitric oxide (NO) and superoxide anion (O(2)(*-), we measured NO production, using a NO chemiluminescence analyzer, and nitric oxide synthase (NOS) activity, monitoring the conversion of L- [14C] arginine to L- [14C] citrulline, and O(2)(*-) by a fluorescence assay using a fluorescence spectrophotometer with hydroethidine (HE) in human pulmonary artery endothelial cells (HPAEC). NO production and eNOS were increased significantly when HPAEC were incubated with 10 microM Lx, and this effect was inhibited by L-NMMA or in the absence of extracellular Ca2+. Addition of 10 mM HE to the cell suspension spontaneously and continuously caused a subtle increase in fluorescence intensity, due to intracellular oxidation of HE to ethidium bromide (EB). Treatment of the cell suspension with Lx after the addition of HE exerted a dose-dependent increase in intracellular EB fluorescence. Pre-treatment with allopurinol, a xanthine oxidase inhibitor, decreased the intracellular EB fluorescence by 54% in HPAEC incubated with 100 microM Lx. These results show that Lx induces NO production via activation of eNOS and O(2)(*-) production in endothelial cells via activation of cellular xanthine oxidase. Thus, Lx is a bioactive lipid.