In vitro uptake of HDL-SAA by tissue macrophages during the development of AA amyloidosis in mice

Hebert, Lise; Janousek, Jaromir; Gervais, Francine

doi:10.3109/13506129508999007

Cited by 4 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ham et al [18] have found that mØ obtained from C57BL/6 mice, in contrast to those obtained from A/J mice, show an intermittent block in the degradation of SAA as analyzed by in vitro degradation experiments with HDL SAA . In contrast, the SAA-degradative capacity of mØ obtained from mice undergoing an amyloidosis induction protocol showed no difference from that of mØ obtained from healthy control animals [20]. Although it appears that the degradative capacity of mØ is influenced by their orgin and not by the amyloid induction protocol, neither of the two studies investigated the pathway by which SAA was degraded and whether mØ from C57BL/6 and A/J mice apply different pathways to degrade SAA [18,20].…”

Section: Discussionmentioning

confidence: 84%

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Röcken

Kisilevsky

1998

Virchows Archiv

View full text Add to dashboard Cite

Serum amyloid A (SAA) is a plasma acute phase protein and the precursor of the AA-fibril protein deposited in AA-amyloidosis. SAA is bound mainly to high-density lipoproteins (HDL(SAA)). Previous investigations have demonstrated that peritoneal macrophages (mO) from mice are capable of binding and endocytosing HDL(SAA). This observation may indicate a pathway by which SAA enters the mO and where its intracellular metabolism may be followed by degradation and/or amyloidogenesis. Since binding and internalization defects of lipoproteins may be associated with different diseases, it is possible that mouse strain susceptibility to amyloidosis is associated with qualitative differences in the binding and internalization of HDL(SAA). To test this hypothesis a series of binding and internalization experiments was performed in vitro with mO from four different mouse strains, CD-1, A/J, C57BL/6J and C3H/HeJ, which differ in their susceptibility to AA-amyloidosis. Using colloidal gold-labelled lipoproteins, it was evident by light and electron microscopy that mO from all four mouse strains are capable of binding and internalizing HDL (without SAA) and HDL(SAA). HDL and HDL(SAA) were found in such compartments of the receptor-mediated pathway as coated pits, coated vesicles, endosomes and multivesicular bodies and in lipid droplets; no qualitative differences were observed. Therefore, it is unlikely that a defect in binding and uptake of HDL(SAA) is related to the different susceptibilities of these mouse strains to develop AA-amyloidosis. However, the results do not exclude the possibility that differences in the intracellular processing of SAA following endocytosis of HDL(SAA) is involved in this differing susceptibility.

show abstract

Section: Discussionmentioning

confidence: 84%

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Röcken

Kisilevsky

1998

Virchows Archiv

View full text Add to dashboard Cite

show abstract

“…The phenotypic variation seen between these two strains of mice could result from a difference in the ability of the cells of the reticuloendothelial system to degrade the amyloid precursor efficiently. We have previously shown that freshly purified splenic macrophages from resistant and susceptible animals had a similar ability to uptake HDL-SAA [19]. Moreover, macrophages obtained from amyloidotic animals displayed a similar ability to uptake HDL-SAA when compared to macrophages obtained from normal non-amyloidotic animals, demonstrating that a difference in SAA degradation is independent of SAA uptake.…”

Section: Discussionmentioning

confidence: 91%

“…Bone marrow-derived macrophages demonstrated a greater ability to degrade HDL-SAA compared to fresh splenic macrophages. Indeed, using fresh tissue macrophages, we have previously reported [19] that a maximum of 20% decrease in the HDL-SAA content of the supernatant was obtained in a 72 h incubation period while macrophage cell lines were found to be capable of reducing to 60% the total amount of HDL-SAA added to the culture medium during the same time period.…”

Section: Degradation Of Saa By Macrophage Cell Linesmentioning

confidence: 99%

“…These observations led to the suggestion that tissue amyloid deposition may be due to a defective SAA degradation by cells of monocytic origin, leading to the accumulation of AA fibrils in specific organs. We have recently determined the ability of freshly isolated spleen and liver macrophages to uptake SAA when incubated in vitro with an HDL-SAA preparation [19]. No difference in SAA uptake was observed when tissue macrophages were obtained from normal or amyloidotic animals, suggesting that if there is a change in the processing of the HDL-SAA by macrophages during amyloidogenesis, this modification would not be at the level of SAA uptake.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

et al. 1997

View full text Add to dashboard Cite

1997;45:354-360 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-g (IFN-g) hampered the precursor degradation suggesting that the activation process may favour extracellular accumulation of the precursor leading to a partial degradation and fibril formation.

show abstract

“…In this study internalization of r‐apoSAA by peritoneal macrophages was not detectable, although the amount of apoSAA in the incubate rapidly decreased and was significantly less than when splenic macrophages were incubated with r‐apoSAA. On the other hand, an increase in vitro of uptake of HDL‐associated apoSAA by splenic macrophages during the development of AA amyloidosis in mice has been reported [37].…”

Section: Discussionmentioning

confidence: 99%

Catabolism of Lipid‐Free Recombinant Apolipoprotein Serum Amyloid A by Mouse Macrophages In Vitro Results in Removal of the Amyloid Fibril‐Forming Amino Terminus

et al. 1998

View full text Add to dashboard Cite

Serum amyloid A fibrils are formed when the normally rapid catabolism of the acute-phase reactant apolipoprotein serum amyloid A (apoSAA) is incomplete; thus amyloidosis may be viewed as a condition of dysregulated proteolysis. There is evidence that apoSAA is dissociated from plasma high-density lipoprotein (HDL) prior to fibril formation. The objective of this study was to investigate degradation of lipid-free apoSAA by tissue macrophages derived from amyloid-susceptible CBA/J mice in vitro. Peritoneal macrophages derived from untreated (normal) mice converted apoSAA (12 kDa) to a single 4 kDa C-terminal peptide while splenic macrophages converted apoSAA to 10, 7 and 4 kDa C-terminal peptides and a 4 kDa peptide that lacked the C- and N-terminal regions. Similar patterns of proteolysis occurred when peritoneal and splenic macrophages from amyloidotic CBA/J mice were used. Conditioned medium prepared from peritoneal, but not splenic macrophages, degraded apoSAA. Specific sites of cleavage indicated activity of cathepsin G- and elastase-like neutral proteases. The data indicate that lipid-free apoSAA can be degraded by secreted or cell-associated neutral proteases that are generated by macrophages to yield peptides that lack fibrillogenic potential.

show abstract

In vitro uptake of HDL-SAA by tissue macrophages during the development of AA amyloidosis in mice

Cited by 4 publications

References 24 publications

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

Catabolism of Lipid‐Free Recombinant Apolipoprotein Serum Amyloid A by Mouse Macrophages In Vitro Results in Removal of the Amyloid Fibril‐Forming Amino Terminus

Contact Info

Product

Resources

About