Low neutral endopeptidase levels in bronchoalveolar lavage fluid of lung cancer patients

Neutral endopeptidase (NEP) is a cell surface enzyme found in normal human lung and which hydrolyzes small bioactive peptides, some of which act as gr owth factors for normal and malignant airway epithelial cells. Expression o f NEP varies widely in human lung tissue from different individuals. NEP is often expressed at low or undetectable levels in both small-cell and non-s mall-cell lung cancer, and inhibits the growth of lung cancer cell lines. V ariation in the expression of NEP could be a factor in susceptibility to lu ng cancer. We hypothesized that NEP could be measured in bronchoalveolar la vage fluid (BALF) and that airway levels of NEP would be low in lung cancer patients as compared with normal controls. We measured NEP and total prote in in cell-free BALF supernatant, and expressed the respective concentratio ns as a ratio. NEP levels showed wide variation in BALF of healthy voluntee rs. Most patients with lung cancer had no NEP detectable in BALF. The mean NEP/total protein ratio was significantly lower in patients with lung cance r (0.87 +/- 0.7 ng NEP/mg protein) than in normal healthy subjects (14.0 +/ - 4.3, p < 0.0003). We conclude that NEP levels are highly variable in BALF of normal volunteers, and are low or undetectable in most BALF specimens f rom patients with lung cancer. Low NEP levels in the airways may be a facto r in the pathogenesis of carcinoma of the lung.