TY - JOUR
T1 - Identification of two zinc metalloendopeptidases in alveolar macrophages of rats, guinea pigs, and human beings
AU - Lesser, Marvin
AU - Fung, Karen
AU - Choi, Ho soon H.
AU - Yoo, Ok Hi
AU - Cardozo, Christopher
PY - 1992/10
Y1 - 1992/10
N2 - Neutral endopeptidases EC 3.4.24.11 and EC 3.4.24.15, widely distributed zinc metalloendopeptidases, degrade a number of biologically active peptides including substance P, bradykinin, neurotensin, and luteinizing hormone-releasing hormone. In this study we measured EC 3.4.24.11 and EC 3.4.24.15 activity in alveolar macrophages, key inflammatory cells in the lung that produce and respond to a large number of bioactive substances including chemotactic peptides, with the substrates glutaryl-ala-ala-phe-2-naphthylamide and tertiary butoxycarbonyl-phe-ala-ala-phe-paraaminobenzoate, respectively. We found that specific activity of EC 3.4.24.15, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-ala-ala-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from Sprague-Dawley rats (485 ± 123 nmol/mg protein · hr) than in cells from Hartley guinea pigs (138 ± 94 nmol/mg protein · hr), healthy human male smokers (121 ± 73 nmol/mg protein · hr) and healthy human male nonsmokers (94 ± 12). In contrast, activity of EC 3.4.24.11, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from human smokers (689 ± 167 nmol/mg protein · hr) and nonsmokers (762 ± 136 nmol/mg protein · hr) than in cells from rats (52 ± 12 nmol/mg protein · hr) and guinea pigs (34 ± 14 nmol/mg protein · hr). An additional activity in alveolar macrophages toward tertiary butorycarbonyl-phe-ala-ala-phe-paraaminobenzoate was inhibited with l-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanido)butane, a specific inhibitor of cysteine proteinases, a finding of interest because in general enzymes in this class show little activity at neutral pH. Alveolar macrophages contain EC 3.4.24.11 and EC 3.4.24.15 and there are significant differences among species in enzyme levels within these cells. Alveolar macrophages may participate in the metabolism of bioactive peptides in vivo through the activities of these two enzymes.
AB - Neutral endopeptidases EC 3.4.24.11 and EC 3.4.24.15, widely distributed zinc metalloendopeptidases, degrade a number of biologically active peptides including substance P, bradykinin, neurotensin, and luteinizing hormone-releasing hormone. In this study we measured EC 3.4.24.11 and EC 3.4.24.15 activity in alveolar macrophages, key inflammatory cells in the lung that produce and respond to a large number of bioactive substances including chemotactic peptides, with the substrates glutaryl-ala-ala-phe-2-naphthylamide and tertiary butoxycarbonyl-phe-ala-ala-phe-paraaminobenzoate, respectively. We found that specific activity of EC 3.4.24.15, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-ala-ala-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from Sprague-Dawley rats (485 ± 123 nmol/mg protein · hr) than in cells from Hartley guinea pigs (138 ± 94 nmol/mg protein · hr), healthy human male smokers (121 ± 73 nmol/mg protein · hr) and healthy human male nonsmokers (94 ± 12). In contrast, activity of EC 3.4.24.11, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from human smokers (689 ± 167 nmol/mg protein · hr) and nonsmokers (762 ± 136 nmol/mg protein · hr) than in cells from rats (52 ± 12 nmol/mg protein · hr) and guinea pigs (34 ± 14 nmol/mg protein · hr). An additional activity in alveolar macrophages toward tertiary butorycarbonyl-phe-ala-ala-phe-paraaminobenzoate was inhibited with l-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanido)butane, a specific inhibitor of cysteine proteinases, a finding of interest because in general enzymes in this class show little activity at neutral pH. Alveolar macrophages contain EC 3.4.24.11 and EC 3.4.24.15 and there are significant differences among species in enzyme levels within these cells. Alveolar macrophages may participate in the metabolism of bioactive peptides in vivo through the activities of these two enzymes.
UR - http://www.scopus.com/inward/record.url?scp=0026461073&partnerID=8YFLogxK
M3 - Article
C2 - 1402335
AN - SCOPUS:0026461073
SN - 0022-2143
VL - 120
SP - 597
EP - 603
JO - Translational Research
JF - Translational Research
IS - 4
ER -