Human Monocyte-derived Macrophages Secrete Two Forms of Proteoglycan-Macrophage Colony-stimulating Factor That Differ in Their Ability to Bind Low Density Lipoproteins
This study evaluated whether human monocyte-derived macrophages synthesize specific types of proteoglycans with lipoprotein-binding capability that could contribute to lipid retention in the arterial wall. After labeling with either [ 35 S]SO 4 or [ 35 S]methionine, macrophages secreted a high molec...
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Veröffentlicht in: | The Journal of biological chemistry 1998-06, Vol.273 (26), p.15985-15992 |
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Zusammenfassung: | This study evaluated whether human monocyte-derived macrophages synthesize specific types of proteoglycans with lipoprotein-binding
capability that could contribute to lipid retention in the arterial wall. After labeling with either [ 35 S]SO 4 or [ 35 S]methionine, macrophages secreted a high molecular mass proteoglycan, with glycosaminoglycan chains of â¼18 kDa and core protein
bands of â¼100 and 55 kDa. Both core protein bands were recognized by an antibody to PG-100, an antibody that recognizes the
proteoglycan form of macrophage colony-stimulating factor (PG-100/PG-MCSF). The interaction between PG-100/PG-MCSF and low
density lipoproteins (LDL) was examined by gel mobility shift. In this system, PG-100/PG-MCSF was resolved further into two
forms. The two forms had the same core proteins but differed in their overall size and glycosaminoglycan content. The larger
form contained glycosaminoglycan chains that were entirely chondroitin ABC lyase-sensitive, whereas the smaller form contained
chains that were sensitive to both chondroitin ABC lyase and heparinase. Both forms bound native LDL with high affinity, but
the larger form bound LDL with higher affinity than the smaller form. The glycosaminoglycan chains of PG-100/PG-MCSF, but
not the core proteins, were responsible for binding to native LDL. Mildly oxidized LDL and methyl-LDL, which have an electrophoretic
charge similar to that of native LDL, also bound PG-100/PG-MCSF. In contrast, extensively oxidized LDL and acetyl-LDL, which
are more electronegative than native LDL, did not bind to either form of PG-100/PG-MCSF. The demonstration of two forms of
human monocyte-derived macrophage PG-100/PG-MCSF which bind LDL may represent an additional role for macrophages in the extracellular
trapping of lipoproteins in atherosclerosis. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.273.26.15985 |