Inhibition of human leukocyte elastase by mineral dust particles.
After isolation, purification, and radiolabeling of elastin from baboon aorta and lung, the rates of hydrolysis of both 3H-labeled elastins by porcine pancreatic elastase (PPE or by human leukocyte elastase (HLE) were compared. PPE (30 nM) degraded aorta and lung elastins at rates of 40 and 75 micrograms/h, respectively, leading to their complete solubilization. In contrast, the low rate of hydrolysis of lung elastin (10 micrograms/h) by HLE was paradoxically accompanied with a fivefold decrease in the Michaelis constant value and became negligible after 1 h of incubation. 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 potential of HLE toward lung elastin. Investigations were carried out to explain why baboon lung elastin exhibited low susceptibility to hydrolysis by HLE. Solubilization of lung elastin with PPE produced a residue that exhibited inhibitory capacity toward HLE when either 3H-labeled aorta elastin or succinyl trialanine nitroanilide was used as a substrate. When analyzed by transmission electron microscopy, this residue was found to consist of several mineral dust particles, mainly kaolinite (53%) of environmental origin. The HLE-inhibitory capacities of various mineral or coal mine dust particles were then analyzed. Mineral aluminium-silicate dusts were found to be potent HLE inhibitors: 5 micrograms of either kaolinite or montmorillonite totally abolished the activity of 0.45 micrograms of HLE. All these results allowed us to propose that HLE inhibition by aluminium-silicate dusts may be of importance in the pathogenesis of industrial pneumoconiosis and in opportunistic lung infections.
Oberson
D
D
Laboratoire de Biologie du Tissu Conjonctif, ER 74 Centre National de la Recherche Scientifique, Faculté de Médecine, Créteil, France.
Desfontaines
L
L
Pezerat
H
H
Hornebeck
W
W
Sebastien
P
P
Lafuma
C
C
D000818:Animals; D001011:Aorta / Q000378:metabolism; D004391:Dust; D004549:Elastin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008903:Minerals / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism / Q000494:pharmacology; D010215:Papio; D012995:Solubility; D013552:Swine
D004391:Dust; D008903:Minerals; D004549:Elastin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase