Am. J. Respir. Crit. Care Med., Vol 150, No. 4, 10 1994, 1026-1031.
Ozone, but not nitrogen dioxide, fragments elastin and increases its susceptibility to proteolysis
RS Winters, BA Burnette-Vick and DA Johnson
Department of Biochemistry, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City 37604.
The effects of ozone (O3) and nitrogen dioxide (NO2) on the solubility and
proteolytic susceptibility of elastin were examined to better understand
how these oxidant air pollutants might damage the lung. In vitro O3
exposures at pH 7.4 resulted in the complete solubilization of elastin, but
NO2 had no effect on solubility. The initial solubilization rate was 65
micrograms/mumol of O3, which increased to 150 micrograms/mumol in the
midregion of a sigmoidal solubilization curve. Peptide fragments of the
O3-solubilized elastin ranged in size from 5 to 20 kD. The conversion of
insoluble elastin into soluble fragments by O3 was not due to the
destruction of desmosine crosslinks. The effect of O3 on the proteolytic
susceptibility of elastin was measured using insoluble elastin recovered
from exposures that resulted in 5.3%, 12.8%, and 26.3% solubilization.
Human neutrophil elastase (HNE) digested the remaining insoluble elastin
samples 4.3, 6.0, and 9.8 times faster than unexposed elastin. In contrast,
NO2-exposed elastin was no more susceptible to digestion by HNE. Ascorbate,
EDTA, and uric acid reduced the proteolytic susceptibility of O3-exposed
elastin, but mannitol afforded no protection. These findings indicate that
the inhalation of O3 may contribute to lung disease by directly damaging
elastin and by increasing its susceptibility to proteolysis, whereas NO2
probably damages lungs via alternative mechanisms.
