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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 414-418

High Levels of Exhaled Nitric Oxide (NO) and NO Synthase III Expression in Lesional Smooth Muscle in Lymphangioleiomyomatosis

Raed A. Dweik, Daniel Laskowski, Metin Özkan, Carol Farver, and Serpil C. Erzurum

Departments of Pulmonary and Critical Care Medicine, Pathology, and Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio

Smooth-muscle proliferation is the hallmark of lymphangioleiomyomatosis (LAM). Although little is known about the pathogenesis of LAM, nitric oxide (NO) is a key regulator of smooth-muscle proliferation. NO is linked to the pathogenesis of other lung diseases such as asthma, in part by the finding of higher-than-normal levels of exhaled NO. If NO were involved in the abnormal smooth-muscle proliferation in LAM, we reasoned that exhaled NO from individuals with LAM would also differ from that of healthy control subjects. To evaluate this hypothesis, we studied exhaled NO in individuals with LAM in comparison with healthy and asthmatic women using a chemiluminescent NO analyzer. Women with LAM had higher exhaled NO than did healthy women but lower than asthmatic women (NO [parts per billion] median (25 to 75%): LAM 8 [7 to 15] [n = 28], control 6 [5 to 8] [n = 21], asthma 14 [8 to 25] [n = 22]; Kruskal-Wallis P < 0.001). Immunohistochemical studies on formalin-fixed, paraffin-embedded sections of surgical and autopsy material from lungs of individuals with LAM showed diffuse NO synthase III (NOSIII) expression in the lesional smooth muscle of LAM similar to that in the vascular endothelium. NOSIII expression was limited to the vascular endothelium and bronchial smooth muscle in healthy control lungs. The increased NO and the presence of NOSIII expression in lesional smooth muscle warrants further study into the potential role for NO in the pathogenesis of LAM.

Abbreviations: diffusion capacity, DLCO; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC; lymphangioleiomyomatosis, LAM; nitric oxide, NO; NO synthase, NOS; neuronal NOS, NOSI; inducible NOS, NOSII; endothelial NOS, NOSIII; parts per billion, ppb; standard error of the mean, SEM.




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