Dipeptidyl peptidase IV in mammalian lungs.

Endothelial cells of the pulmonary circulation are equipped with an ectoenzyme protease system on their luminal surface. The membrane-bound proteases act on the circulating polypeptides and cleave certain peptide bonds in their structure, thus modifying their biological properties. We studied the enzyme dipeptidyl peptidase IV (DP-IV) in mammalian lungs in order to elucidate its contribution to the aforementioned proteolytic processing. We have found that lungs of mammalian species posses DP-IV with different levels of specific activity. In rat lungs the specific activity of DP-IV progressively increased during development between the 18th fetal and the 70th postnatal days. Human embryonal and fetal lungs had significantly higher specific activity of DP-IV compared with the lungs of adult individuals. The enzyme in lungs was mainly membrane bound and was solubilized by some detergents, but not with papain and trypsin. The Triton X-100-solubilized DP-IV from rat lung lysosomal-microsomal membranes migrated during electrophoresis on continuous 4–30% gradient polyacrylamide gel at native apparent Mr values of 260 000 and 490 000. Using a histochemical technique we found the enzyme activity of DP-IV in the capillary bed of the lung alveolar septa only. Four aminoacyl-L-proline-4-nitroanilide substrates for DP-IV were cleaved rapidly during one passage through isolated perfused blood-free rat lungs. The perfusion profiles of cleavage of these substrates were largely coincident with that of Blue Dextran 2 000, a compound, which is unlikely to leave the intravascular space. Taken together, the data suggest that DP-IV operates in vivo as a membrane-bound ectoenzyme on the luminal surface of pulmonary endothelial cells and that it may cleave certain circulating polypeptides.