The Effect of Crystal Structure on Mouse Lung Inflammation and Fibrosis

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Abstract
In order to identify the physical and structural parameters that relate best to the membranolytic, inflammatory, and fibrotic potentials of different silicon dioxide (SiO2) and titanium dioxide (TiO2) crystals, we have studied the potential of four different SiO2 and two different TiO2 crystal structures to lyse human red blood cells and to induce pulmonary inflammation and fibrosis in mice. The crystals studied were quartz, tridymite, cristobalite, coesite, anatase, and rutile. Mice were injected intratracheally with each crystal at constant surface area. Inflammation and fibrosis were assessed 6 wk after crystal instillation by wet lung weight (lung index), protein concentration of lung lavage fluid, the level of hydroxyproline in the lung, and histologic examination. In vitro red blood cell (RBC) lysis was evaluated by incubating the cystals with 51Cr-labeled RBC and measuring the release of 15Cr into the medium. Known crystallographic data for each of the minerals were used to calculate the percent occupied volume. Biologic activity seemed to correlate with percent occupied volume, suggesting that surface molecular topology may be important in crystal-cell interactions. The crystals with more irregular surfaces and protruding oxygen atoms, which form surface pockets (quartz, tridymite, and cristobalite), showed a dramatic increase over saline controls for lung index (> 2 .times.), cell number and lavage protein concentration (> 4 .times.), and hydroxyproline level (> 2 .times.). The other more boxlike crystals (coesite, anatase, and rutile) displayed little change in these parameters. This trend was also observed in the RBC lysis date. The molecular modeling of the crystals'' surfaces has suggested that the spatial configuration of the surface oxygen atoms may be an important parameter in determining a crystal''s biologic activity.