COMPARISON OF THE BINDING AND ENDOCYTOSIS OF HIGH-DENSITY-LIPOPROTEINFROM HEALTHY (HDL) AND INFLAMED (HDLSAA) DONORS BY MURINE MACROPHAGESOF 4 DIFFERENT MOUSE STRAINS

Serum amyloid A (SAA) is a plasma acute phase protein and the precurso r of the AA-fibril protein deposited in AA-amyloidosis. SAA is bound m ainly to high-density lipoproteins (HDLSAA). Previous investigations h ave demonstrated that peritoneal macrophages (mdiameter) from mice are capable of binding and endocytosing HDLSAA. This observation may indi cate a pathway by which SAA enters the mdiameter and where its intrace llular metabolism may be followed by degradation and/or amyloidogenesi s. Since binding and internalization defects of lipoproteins may be as sociated with different diseases, it is possible that mouse strain sus ceptibility to amyloidosis is associated with qualitative differences in the binding and internalization of HDLSAA. To test this hypothesis a series of binding and internalization experiments was performed in v itro with mdiameter from four different mouse strains, CD-I, A/J, C57B L/6J and C3H/HeJ, which differ in their susceptibility to AA-amyloidos is. Using colloidal gold-labelled lipoproteins, it was evident by ligh t and electron microscopy that mdiameter from all four mouse strains a re capable of binding and internalizing HDL (without SAA) and HDLSAA. HDL and HDLSAA were found in such compartments of the receptor-mediate d pathway as coated pits, coated vesicles, endosomes and multivesicula r bodies and in lipid droplets; no qualitative differences were observ ed. Therefore, it is unlikely that a defect in binding and uptake of H DLSAA is related to the different susceptibilities of these mouse stra ins to develop AA-amyloidosis. However, the results do not exclude the possibility that differences in the intracellular processing: of SAA following endocytosis of HDLSAA is involved in this differing suscepti bility.