INHIBITION OF HUMAN-LEUKOCYTE ELASTASE BY MINERAL DUST PARTICLES

After isolation, purification, and radiolabeling of elastin from baboo n aorta and lung, the rates of hydrolysis of both H-3-labeled elastins by porcine pancreatic elastase (PPE) or by human leukocyte elastase ( HLE) were compared. PPE (30 nM) degraded aorta and lung elastins at ra tes of 40 and 75 mu g/h, respectively, leading to their complete solub ilization. In contrast, the low rate of hydrolysis of lung elastin (10 mu g/h) by HLE was paradoxically accompanied with a fivefold decrease in the Michaelis constant value and became negligible after 1 h of in cubation. Moreover, HLE adsorption isotherms showed that 0.87 nmol HLE was adsorbed on 1 mg of aorta elastin vs. 1.30 nmol/mg lung elastin. Also, increasing ionic strength was found to enhance the elastolytic p otential of HLE toward lung elastin. Investigations were carried out t o explain why baboon lung elastin exhibited low susceptibility to hydr olysis by HLE. Solubilization of lung elastin with PPE produced a resi due that exhibited inhibitory capacity toward HLE when either H-3-labe led aorta elastin or succinyl trialanine nitroanilide was used as a su bstrate. When analyzed by transmission electron microscopy, this resid ue was found to consist of several mineral dust particles, mainly kaol inite (53%) of environmental origin. The HLE-inhibitory capacities of various mineral or coal mine dust particles were then analyzed. Minera l aluminum-silicate dusts were found to be potent HLE inhibitors: 5 mu g of either kaolinite or montmorillonite totally abolished the activi ty of 0.45 mu g of HLE. All these results allowed us to propose that H LE inhibition by aluminum-silicate dusts may be of importance in the p athogenesis of industrial pneumoconiosis and in opportunistic lung inf ections.