Selective localization of murine ApoSAA(1)/SAA(2) in endosomes-lysosomes in activated macrophages and their degradation products

Murine ApoSAA(3) is synthesized and secreted by activated monocytoid cells. In contrast, these cells have been implicated in the endocytosis of exogenous murine apoSAA(1)/SAA(2) and in AA amyloid formation. The implication is that endocytosed apoSAA(1)/SAA(2) may be processed in the endosomes-lysosomes (EL). Here we show the topographic relationship between apoSAA3 and apoSAA(1)/SAA(2) and identify apoSAA(1)/SAA(2) and their derivatives in peritoneal macrophages from alveolar hydatid cyst infected mice undergoing amyloidosis. Confocal microscopy localized apoSAA(1)/SAA(2) exclusively to the EL whereas apoSAA(3) generally had a non-vesicular cytoplasmic distribution. Immunoblotting of the macrophage cytoplasmic fractions, regardless of the duration of the infection, identified predominantly two similar to 5 and 12 kDa C-terminus cleaved apoSAA(1)/SAA(2) derivatives which resembled in molecular mass the tissue AA. Immunoblotting of the infected mouse sera did not reveal any apoSAA(1)/SAA(2) derivatives. These data suggest that following endocytosis, apoSAA(1)/SAA(2) is most likely partially degraded and retained in the EL. Thus, the possibility remains that during chronic inflammation, all or a portion of the C-terminus cleaved apoSAA(1)/SAA(2) under low pH conditions in the El, may transform into ''nascent'' AA.