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.
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.
Röcken
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Department of Pathology, Queen's University and The Syl and Molly Apps Medical Research Centre, Kingston General Hospital, Ontario, Canada.
Kisilevsky
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D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D017979:Gold Colloid; D008075:Lipoproteins, HDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013045:Species Specificity
D001053:Apolipoproteins; D017979:Gold Colloid; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein