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 c ells. 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 relationshi p between apoSAA3 and apoSAA(1)/SAA(2) and identify apoSAA(1)/SAA(2) a nd their derivatives in peritoneal macrophages from alveolar hydatid c yst infected mice undergoing amyloidosis. Confocal microscopy localize d apoSAA(1)/SAA(2) exclusively to the EL whereas apoSAA(3) generally h ad a non-vesicular cytoplasmic distribution. Immunoblotting of the mac rophage cytoplasmic fractions, regardless of the duration of the infec tion, 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 reve al any apoSAA(1)/SAA(2) derivatives. These data suggest that following endocytosis, apoSAA(1)/SAA(2) is most likely partially degraded and r etained in the EL. Thus, the possibility remains that during chronic i nflammation, all or a portion of the C-terminus cleaved apoSAA(1)/SAA( 2) under low pH conditions in the El, may transform into ''nascent'' A A.