SILICA-INDUCED APOPTOSIS IN ALVEOLAR AND GRANULOMATOUS CELLS IN-VIVO

Silica is a 'toxicanr: that can stimulate cells to produce various cel lular products such as free radicals, cytokines, and growth factors. S ilica and its induced substances may induce apoptosis to regulate the evolution of silica-induced inflammation and fibrosis. To examine this hypothesis, groups of Wistar male rats were intratracheally instilled with different doses oi Min-U-Sil 5 silica (Silica, Berkeley Springs, WV). Ten days after the instillation, we obtained cells by bronchoalv eolar lavage and placed them on slides by cytospin preparation. The sl ides were stained with Diff-Quik (Lab Aids, Sydney, NSW, Australia) an d examined under oil immersion. A substantial number of cells with apo ptotic features were identified in all silica-instilled rats and the a poptosis was confirmed by agarose gel electrophoresis. The number oi a poptotic cells was clearly related to silica dosage. Engulfment of apo ptotic cells by macrophages was also noted. Neutrophil influx in silic a-instilled rats could be saturated with the increase of silica dosage and the number of macrophages in different dose groups changed in par allel with the proportion of apoptotic cells. Fifty-six days after ins tillation, morphologically apoptotic cells could he identified in gran ulomatous cells of lung tissue from silica-instilled rats. We conclude that intratracheal instillation of silica could induce apoptosis in b oth alveolar and granulomatous cells, end the apoptotic change and sub sequent engulfment by macrophages might play a role in the evolution o f silica-induced effects.