Elastase inhibitors in sputum from bronchitic patients with and without α1-proteinase inhibitor deficiency: partial characterization of a hitherto unquantified inhibitor of neutrophil elastase

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Abstract
1. Anti-elastase function in sputum sol-phase from patients with α1-proteinase inhibitor (α1PI) deficiency was compared with sol-phase from patients with cigarette smoke-induced bronchitis and emphysema. 2. Both α1PI (2P < 0.01) and anti-leucoprotease (ALP) (2P < 0.01) concentrations were lower in sol-phase from the α1PI-deficient group, although α2-macroglobulin (α2M) levels were similar. 3. There was no difference in α1PI function between the two groups, but the inhibitor was only ≃ 30% active. 4. The absolute neutrophil elastase (NE) inhibitory capacity was similar in both groups (median 185 μg of NE inhibited/ml of sputum, range 80–480, for the α1PI-deficient group; median 175, range 80–300, for the bronchitic group). A substantial proportion of NE inhibition in secretions could not be accounted for by the amount of α1PI, ALP and α2M present (median 74.8%, range 43.2–97.4, for α1PI-deficient sol-phase; median 50.0%, range 0–80.8, for bronchitic sol-phase). 5. Gel filtration of sol-phase demonstrated the presence of NE inhibition in the low molecular weight fractions which was markedly sensitive to changes in substrate concentration and ionic strength, in contrast to purified α1PI and ALP. 6. Sputum sol-phase from both groups failed to prevent hydrolysis of elastin–fluorescein or succinyltrialanyl-p-nitroanilide by NE completely during prolonged incubation in the presence of an excess of functional inhibitors. This was more apparent in secretions from subjects with α1PI deficiency and may explain why such patients have a more rapidly progressive form of emphysema.