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

Abstract

Expression of heme-oxygenuse-I (HO-I), an important marker of oxidative stress, has been studied extensively in the context of Alzheimer's disease. Evidence of HO-I expression during AA amyloidosis is, at best, sketchy. We present comparative data on HO-I 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-I expression in heputo-splenic reticuloendothelial (RE) cells of the AHC-infected mice prior and during AA fibril deposition. Based on the cumulative data, we conclude that HO-I 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-I 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 immunocytochernically 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-I expression in RE cells; the potential role of inflammatory cytokines in HO-I response need to be investigated further.

Key Words:

• alveolar hydatid cyst
• heme-oxygenase
• oxidative stress
• AA amyloid
• serum amyloid A
• image analysis
• western blotting
• immunohistochemistry