DIMINISHED ARACHIDONIC-ACID METABOLITE RELEASE BY BOVINE ALVEOLAR MACROPHAGES EXPOSED TO SURFACE-MODIFIED SILICA

Modification of the silica surface has been shown to reduce its cytotoxicity in vitro and its fibrogenic activity in vivo. We have shown silica to be a potent stimulator of arachidonic acid (AA) metabolism in bovine alveolar macrophages (BAM). To determine the effect of surface-modified silica on AA metabolism in BAM, we exposed BAM in vitro to silica treated with aluminum lactate or polyvinylpyridine-N-oxide (PVPNO). BAM were prelabeled with [H-3]AA and incubated with 3 and 5 mg of silica. Unmodified silica at these doses elicited maximal AA metabolite release from BAM. AA metabolites were analyzed by high performance liquid chromatography. Lactate dehydrogenase release was quantitated to determine the cytotoxicity of treated and untreated silica on BAM. Treating silica with aluminum lactate or PVPNO significantly (P less-than-or-equal-to 0.05) reduced 5-lipoxygenase metabolite release and significantly (P less-than-or-equal-to 0.05) increased cyclooxygenase metabolite release. These changes in AA metabolite release were accompanied by a significant (P less-than-or-equal-to 0.05) reduction in the cytotoxicities of the treated silicas compared with untreated silica. Our results suggest that the reduced inflammatory and fibrogenic activity of surface-modified silica may in part be due to reduced AA metabolite release from exposed macrophages.