Inhalation of
silicates induces a variety of
lung diseases in humans. The molecular mechanism(s) by which these dusts cause disease is not known. Because several naturally occurring
mineral oxides have large amounts of transition
metal ions on their surfaces, we tested the hypothesis that surface complexation of
iron may be an important determinant of their ability to induce disease.
Silica,
crocidolite,
kaolinite, and
talc complexed considerable concentrations of Fe3+ onto their surfaces from both in vitro and in vivo sources. The potential
biological importance of
iron complexation was assessed by examining the relationship between surface [Fe3+] and the ability of
silicates to mediate oxidative degradation of
deoxyribose in vitro, induce a respiratory burst and elicit
leukotriene B4 (
LTB4) release by alveolar macrophages (AM) in vitro, and cause acute alveolitis after intratracheal insufflation. For these studies, three varieties of
silicate dusts were used:
iron-loaded, wetted (unmodified), and
deferoxamine-treated to remove Fe3+. The ability of
silicates to catalyze
oxidant generation in an ascorbate/H2O2 system in vitro, to trigger respiratory burst activity and
LTB4 release by AM, and to induce acute
lung inflammation in the rat all increased with surface complexed Fe3+. The results of these studies suggest that surface complexation of
iron may be an important determinant in the pathogenesis of disease after
silicate exposure.