Generation of Free Radicals from Freshly Fractured Silica Dust: Potential Role in Acute Silica-Induced Lung Injury

"SUMMARY Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis we propose that these surface features may lead to enhanced manifestations of lung Injury. Grinding of silica produces ~10"" Si and SI-O (silicon-based) radicals per gram of dust on the particulate surface which are characterized by an electron spin resonance (ESR) spectrum centered around g = 2.0015. These silicon-based radicals react with aqueous media to produce OH radicals, which are demonstrable using a DMPO spin trap. The concentration of silicon-based radicals in silica decreases with aging in air and exhibits a half-life of ~30 h, whereas its ability to generate OH radicals in aqueous solution decreases with a half-life of ~20 h. However, on storage in aqueous media, the concentration of silicon-based radicals end the dust's ability to generate OH radicals decrease significantly within a few minutes. Freshly ground silica is also more biologically reactive than aged silica, because freshly crushed silica activates a greater respiratory burst In alveolar macrophages than aged silica, i.e., storage of ground dust in air decreases silica-Induced superoxide anion secretion, hydrogen peroxide release, and NBT reduction by 25%, 68%, and 43%, respectively. Furthermore, compared to aged silica, freshly ground silica exhibits a greater cytotoxic effect on cellular membrane Integrity, i.e., a 1.5-fold increase in LDH release from macrophages, a 36-fold increase in hemolytic activity, and a three-fold increase in the ability to induce lipid peroxidation. Because acute silicosis is frequently associated with occupations in which freshly fractured crystalline silica of respirable size is generated, the present study suggests that fracture-generated silicon-based radicals may play a significant role in the pathogenesis of this disease. AM REV RESPIR DIS 1955; 133:1213-1218IntroductionOccupational exposure to crystalline silica can be associated with either chronic or acute pulmonary disease. Chronic silicosis becomes manifest 20 to 40 years after first exposure and is characterized by development of concentric hyalinized nodular lesions in the lung with the de-velopment of dyspnea over a period of several decades. Acute silicosis, on the other hand, is manifested by a rapid on-set after exposure and is characterized by the accumulation of an amorphous granular lipoprotein exudate in the airspaces and rapid development of respiratory disability within a few years (1-3).Information is growing concerning the etiology of chronic silicosis. Studies sug-gest that several mechanisms may be in-volved in the development of fibrosis. Lung injury may result from silica-induced release of lysosomal enzymes from alveolar macrophages (4, 5). In ad-dition, silica-induced activation of su-peroxide anion and hydrogen peroxide release from alveolar macrophages may result in oxidant-induced damage to lung parenchyma (6). Silica exposure can also result in the release of mediators from alveolar macrophages which enhance the proliferation of fibroblasts and the syn-thesis of collagen by these pneumocytes (7, 8)."