Characterization of a soluble form of neutral endopeptidase-24.11 (EC 3.4.24.11) in human serum: enhancement of its activity in serum of underground miners exposed to coal dust particles.
A previous epidemiological study has reported the elevation of a serum metalloendopeptidase activity for underground coalminers exposed to chronic inhalation of coal mine dust particles. In this work, we have unambiguously characterized this activity as neutral endopeptidase (EC 3.4.24.11) using five different criteria. The apparent molecular weight of 100,000 g mol-1 calculated for the serum peptidase using Western blots or direct binding of the neutral endopeptidase 24.11 inhibitor [125I]-RB104 to the enzyme in acrylamide gels, suggests that the soluble form of this ectoenzyme is not generated by a post-translational cleavage of the membrane-bound form, as is the case for the closely related ectoenzyme, angiotensin-converting enzyme. The circulating endopeptidase very likely results from a shedding process. The increase in serum neutral endopeptidase 24.11 activity of underground miners compared with surface miners (5.7-fold), P < 0.01) is not correlated with systemic inflammation parameters, but seems to reflect the chronic pulmonary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury.
Soleilhac
J M
JM
Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM-URA D1500 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie, Paris, France.
Lafuma
C
C
Porcher
J M
JM
Auburtin
G
G
Roques
B P
BP
D003031:Coal / Q000009:adverse effects; D003032:Coal Mining; D004391:Dust; D006801:Humans; D015151:Immunoblotting; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000097:blood*; D011009:Pneumoconiosis / Q000097:blood* / Q000201:enzymology / Q000453:epidemiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D012995:Solubility; D015244:Thiorphan / Q000031:analogs & derivatives / Q000494:pharmacology
D003031:Coal; D004391:Dust; D011480:Protease Inhibitors; C072559:retrothiorphan; D015244:Thiorphan; D015260:Neprilysin