Heme-oxygenase-1 response, a marker of oxidative stress, in a mouse model of AA amyloidosis.

Expression of heme-oxygenase-1 (HO-1), an important marker of oxidative stress, has been studied extensively in the context of Alzheimer's disease. Evidence of HO-1 expression during AA amyloidosis is, at best, sketchy. We present comparative data on HO-1 response in alveolar hydatid cyst (AHC) infected amyloid sensitive (C57BL/6) and amyloid resistant (CE/J) mouse strains. Histochemical and peroxidase-immunoperoxidase methods were used to monitor serum amyloid A (SAA) and AA fibril deposition and HO-1 expression in hepato-splenic reticuloendothelial (RE) cells of the AHC-infected mice prior and during AA fibril deposition. Based on the cumulative data, we conclude that HO-1 expression corresponded closely with tissue deposition of SAA, but was unrelated to AA fibril deposition. To ascertain whether SAA deposition might act as the trigger for HO-1 expression in the RE cells, macrophages were incubated for up to 72 h with SAA-containing mouse serum. The SAA-treated macrophages, although negative for HO-1 protein, demonstrated SAA in the cell extracts and immunocytochemically in the vacuolar compartments, indicating macrophage-mediated endocytosis and trafficking of SAA. In sum, these results exclude SAA and AA fibrils as the primary triggers in the induction of HO-1 expression in RE cells; the potential role of inflammatory cytokines in HO-1 response need to be investigated further.