Am. J. Respir. Crit. Care Med.,
Volume 159, Number 3, March 1999, 907-910
Low Neutral Endopeptidase Levels in Bronchoalveolar
Lavage Fluid of Lung Cancer Patients
ANDREA J.
COHEN,
WILBUR A.
FRANKLIN,
CATHY
MAGILL,
JULIE
SORENSON,
and
YORK E.
MILLER
Department of Pathology, Denver Veterans' Administration Medical Center; University of Colorado Health Sciences Center; National
Jewish Center for Medicine and Research, Denver, Colorado; and Arris Pharmaceuticals, South San Francisco, California
Neutral endopeptidase (NEP) is a cell surface enzyme found in normal human lung and which hydrolyzes small bioactive peptides, some of which act as growth factors for normal and malignant airway epithelial cells. Expression of 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-small-cell lung cancer, and
inhibits the growth of lung cancer cell lines. Variation in the expression of NEP could be a factor in
susceptibility to lung cancer. We hypothesized that NEP could be measured in bronchoalveolar lavage 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 protein in cell-free BALF supernatant, and expressed the respective concentrations as a ratio. NEP levels showed wide variation in BALF of healthy volunteers. Most patients with lung cancer had no NEP detectable in BALF. The mean NEP/total protein ratio was significantly lower in patients with lung cancer (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 from patients with
lung cancer. Low NEP levels in the airways may be a factor in the pathogenesis of carcinoma of the lung.
