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To determine whether alveolar epithelial cell (AEC) apoptosis via caspase activation is involved in asbestos-induced lung injury, we examined apoptosis, caspase-3 and-9 activation using chrysotile asbestos exposure models in vitro and in vivo.Apoptotic cells were assessed in A549 cells with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method after 48 hours exposure of chrysotile asbestos (5 to 100 ug/cm2). Asbestos exposure induced a dose-dependent increase of apoptotic cells, and both pretreatment with Z-LEHD-FMK (caspase-3 inhibitor) or Z-DEMK-FMK (caspase-9 inhibitor) significantly suppressed asbestos-induced apoptosis. Expression of cleaved caspase-3 and-9 increased significantly from 18 to at least 48 hours after asbestos exposure. In vivo study, either 1 or 2 mg of chrysotile asbestos were administered into rat lungs intratracheally, and the lungs were obtained 3 days, 1 and 2 weeks, 1, 3 and 6 months after the administration. Asbestos exposure increased the number of apoptotic cells and the activation of cleaved caspase-3 and-9 most at 3 days in a dose dependent manner, and continued to increase them until at least 6 months after asbestos exposure. Apoptotic cells and cleaved caspase-3 and-9 positive cells were mainly observed in AECs. These findings suggest that AEC apoptosis via caspase-3 and-9 activation is involved in asbestos-induced lung injury. [ABSTRACT FROM AUTHOR]

In order to elucidate the pathology and mechanism of lung toxicity induced by chronic hair spray inhalation, male Wister rats 9 wk of age were exposed to a uniform concentration of hair spray for up to 12 wk using a jet nebulizer. The aerosol concentration to which the rats were exposed was about 7 g/m 3 . Differential cell counts in bronchoalveolar lavage fluid (BALF), the expression of several cytokines from alveolar macrophage using the reverse-transcription polymerase chain reaction (RT-PCR) method, and histopathologic evaluation using a computer-aided graphic analyzer (IBAS) were conducted 1, 4, 8, and 12 wk after exposure. Over the passage of time, neutrophils and macrophages increased in BALF, and neutrophils infiltrated in the lung interstitium from the peribronchial interstitium to the alveolar septum. Alveolar macrophages showed increased expression of both the mRNA of tumor necrosis factor (TNF)-α and the mRNA of the chemokines macrophage inflammatory protein 2 (MIP2) and cytokine-induced neutrophil attractant (CINC). From these findings, chronic inhalation of hair spray is considered to induce at first intra-alveolar accumulation and activation of alveolar macrophages, followed by recruitment of neutrophils in the lung through the expression of proinflammatory cytokine, CINC, and MIP2, which cause predominantly neutrophilic inflammation in the lung. [ABSTRACT FROM AUTHOR]