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 c hronic inhalation of coal mine dust particles. In this work, we have u nambiguously characterized this activity as neutral endopeptidase (EC 3.4.24.11) using five different criteria. The apparent molecular weigh t of 100 000 g mol(-1) calculated for the serum peptidase using Wester n blots or direct binding of the neutral endopeptidase 24.11 inhibitor [I-125]-RB104 to the enzyme in acrylamide gels, suggests that the sol uble form of this ectoenzyme is not generated by a post-translational cleavage of the membrane-bound form, as is the case for the closely re lated ectoenzyme, angiotensin-converting enzyme. The circulating endop eptidase very likely results from a shedding process. The increase in serum neutral endopeptidase 24.11 activity of underground miners compa red with surface miners (5.7-fold, P < 0.01) is not correlated with sy stemic inflammation parameters, but seems to reflect the chronic pulmo nary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury.