Selective localization of murine ApoSAA1/SAA2in endosomes-lysosomes in activated macrophages and their degradation products

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Abstract
Murine ApoSAA3 is synthesized and secreted by activated monocytoid cells. in contrast, these cells have been implicated in the endocytosis of exogenous murine apoSAA/SAA2 and in AA amyloid formation. The implication is that endocytosed apoSAA1/SAA2 may be processed in the endosomes-lysosomes (EL). Here we show the topographic relationship between apoSAA3 and apoSAA1/SAA2 and identify apoSAA1 /SAA2 and their derivatives in peritoneal macrophages from alveolar hydatid cyst infected mice undergoing amyloidosis. Confocal microscopy localized apoSAA1/SAA2 exclusively to the EL whereas apoSAA3 generally had a non-vesicular cytoplasmic distribution. Immunoblotting of the macrophage cytoplasmic fractions, regardless of the duration of the infection, identified pre-dominantly two ~5 and 12 kDa C-terminus cleaved apoSAA1/SAA2 derivatives which resembled in molecular mass the tissue AA Immunoblotting of the infected mouse sera did not reveal any apoSAA1/SAA2 derivatives. These data suggest that following endocytosis, apoSAA1/SAA2 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/SAA2 under low pH conditions in the EL, may transform into “nascent” AA.