NEUTRAL METALLOENDOPEPTIDASE IN HUMAN-LUNG TISSUE AND CULTURED-CELLS

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Abstract
The distribution of a neutral metalloendopeptidase (NEP), or "enkephalinase," in human lung tissue and cultured cells was compared with that of angiotensin I converting enzyme (ACE). The specific activities of NEP and ACE were measured in homogenates of fetal lung tissue and in isolated airways and pulmonary vessels. NEP activity was highest in airway tissue, and ACE activity was highest in isolated vessels. Human endothelial cells from either umbilical veins or pulmonary arteries had high ACE activity (80 to 90 nmol/h/106 cells) but only a trace of NEP activity (0.5 to 0.6 nmol/h/106 cells). Fibroblasts cultured from human lungs were low in ACE but richer in NEP than cultured endothelial cells. Fibroblasts from human foreskins or caesarean section skin were the richest source of NEP activity (60 to 80 nmol/h/106 cells). Immunohistochemical studies confirmed the biochemcial assays. As expected, ACE was localized on the luminal surface of blood vessels, with a distribution similar to that of factor VIII antigen, an endothelial marker. In contrast, NEP was localized within the alveolar septa. Cultured endothelial cells stained only weakly for NEP in contrast to cultured fibroblasts. The location of these 2 enzymes in different cells and the differences in peptide substrate specificity suggests that they act sequentially on circulating peptides or those released within microvascular beds.