Mechanisms of action of poorly soluble particulates in overload-related lung pathology

For reasons that are unclear, poorly soluble particulates are associated wi th the development of inflammation, fibrogenesis, and carcinogenesis in the rat. The pathogenesis of these changes may be triggered by distinct or spe cies-specific cellular responses to inhaled particulates in a manner simila r to known fibrogenic and carcinogenic fibers, such as asbestos. Data revie wed here suggest that generation of oxidants by poorly soluble particulates is a key factor in the initiation of inflammation and generation of chemok ines and cytokines in the rat. These substances then cause hyperplasia of e pithelial cells and fibroblasts. The diminished or lack of proliferative re sponses by poorly soluble particulates in mice and primates, in comparison to rats, may be reflected by intrinsic differences in their oxidant-generat ing capacities or repair after oxidant injury or DNA damage.