Degradation of amyloid A precursor protein SAA by macrophage cell lines obtained from amyloid resistant and susceptible strains of mice.
Reactive AA amyloidosis can be induced in mice in a model of sustained inflammation following daily casein subcutaneous injections. However, the development of AA amyloidosis is known to vary in different strains of mice. The C57BL/6 strain is susceptible to the development of amyloidosis while the A/J strain is resistant. The degradation of purified serum amyloid A (SAA) protein by human monocytes as well as by mouse macrophages has been shown. The resistance/susceptibility of different mouse strains to the development of systemic amyloidosis may therefore be related to a difference in the ability of macrophages to degrade SAA. The authors have used bone marrow-derived macrophage cell lines obtained from susceptible C57BL/6 (ANA-1) and resistant A/J (A/J 10) mouse strains to compare their ability to degrade HDL-SAA in vitro. Cells were incubated with HDL-SAA for up to 72 h and the culture medium was analysed by SDS-PAGE to determine the rate of SAA degradation by the macrophages. The A/J 10 cells (resistant) were found to initiate a constant HDL-SAA degradation promptly whereas ANA-1 cells (susceptible) showed an intermittent block in the degradation of the precursor. Activation of macrophages by lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma) hampered the precursor degradation suggesting that the activation process may favour extracellular accumulation of the precursor leading to a partial degradation and fibril formation.
Ham
D
D
McGill Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Canada.
Caouras
V
V
Radzioch
D
D
Gervais
F
F
D000686:Amyloidosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells; D002364:Caseins / Q000008:administration & dosage; D002460:Cell Line; D004198:Disease Susceptibility; D007113:Immunity, Innate / Q000235:genetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D002364:Caseins; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein