CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer
membrane of a variety of cells. Because aminopeptidase expression was shown
to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here t
he significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The acti
vity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significa
ntly higher in patients with sarcoidosis than in normal volunteers (NV) and
control patients (CP). The activity significantly correlated with lymphocy
te percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and
was higher in patients with sarcoidosis with parenchymal involvement than
in those without the involvement, CD13/aminopeptidase N protein, which has
a molecular mass of approximately 150 kD, was detectable in alveolar macrop
hages (AM) from patients with sarcoidosis at higher levels than in those fr
om NV. CD13/aminopeptidase N induced in vitro chemotactic migration of huma
n lymphocytes in a concentration range of 10(-5) to 10(-1) U/ml. The chemot
actic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocyt
es. The enzymatic activity of CD13/aminopeptidase N was responsible for the
chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase
N, abolished the chemotactic activity. Higher chemotactic activity for lym
phocytes was detected in the BALF from patients with sarcoidosis than in th
at from NV, and the activity was significantly decreased by treatment with
bestatin. This study indicates that CD13/aminopeptidase N expressed in AM m
ay have a role in T-lymphocyte involvement in the sarcoid lung and the path
ogenesis of alveolitis in this disorder.