Effects of ozone and nitrogen dioxide on human lung proteinase inhibitors

Journal Article · Thu Jan 01 04:00:00 EST 1987 · Research Report Health Effects Institue; (USA)

OSTI ID:5128694

Johnson, D A ^[1]

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1. East Tennessee State Univ., Johnson City (USA)

Based on available knowledge, this study shows that alpha-1-proteinase inhibitor (alpha 1-PI) plays an important role in protecting lung elastin from elastolytic proteinases, particularly human neutrophil elastase (HNE). Studies previous to this one showed that alpha 1-PI was very susceptible to inactivation by oxidants. We sought to use this oxidant sensitivity as an in vivo marker for ozone (O3) and nitrogen dioxide (NO2) exposure. The mechanism of alpha 1-PI inactivation by O3 and NO2 was examined to provide insight concerning the pathogenesis of oxidant-mediated lung damage. Attention also was focused on the bronchial leukocyte proteinase inhibitor (BLPI), which inhibits HNE in the bronchial secretions. Careful examination of blood plasma samples from individuals exposed to 0.5 ppm O3 for four hours on two consecutive days failed to detect any inactivation of alpha 1-PI. This result showed that blood alpha 1-PI was not a satisfactory marker for O3 exposure, but, more importantly, demonstrated that inhaling O3 for short periods does not grossly inactivate this important protein. Studies on BLPI showed that it is a significant inhibitor of HNE and probably plays a more important role in protecting the lung than previously thought. BLPI, like alpha 1-PI, was found to be inactivated by oxidants, including O3 and NO2. The mechanism of O3 inactivation of leukocyte proteinase inhibitors was studied using alpha 1-PI, alpha-1-antichymotrypsin (alpha 1-Achy), BLPI, and Eglin C. While all these inhibitors differed in structure, the concentrations of O3 required for inactivation were essentially the same, except for alpha 1-Achy, which only lost half of its inhibitory activity. It would seem from these results that O3 can damage proteins via the oxidation of any of the following: tryptophan (Trp), methionine (Met), tyrosine (Tyr), or histidine (His) residues.

• OSTI ID: 5128694
• Journal Information: Research Report Health Effects Institue; (USA), Journal Name: Research Report Health Effects Institue; (USA) Vol. 11; ISSN RRHIE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MARKERS
BODY
CHALCOGENIDES
ENZYME INHIBITORS
ENZYMES
FUNCTIONS
HYDROLASES
INHALATION
INTAKE
LUNGS
MAMMALS
MAN
NITROGEN COMPOUNDS
NITROGEN DIOXIDE
NITROGEN OXIDES
ORGANS
OXIDES
OXYGEN COMPOUNDS
OZONE
PEPTIDE HYDROLASES
PRIMATES
RESPIRATORY SYSTEM
SENSITIVITY
SERINE PROTEINASES
TOXICITY
VERTEBRATES