Differentiated macrophages synthesize a heparan sulfate proteoglycan and an oversulfated chondroitin sulfate proteoglycan that bind lipoprotein lipase.
Lipoprotein lipase (LpL), which facilitates lipoprotein uptake by macrophages, associates with the cell surface by binding to proteoglycans (PGs). Studies were designed to identify and characterize specific PGs that serve as receptors for LpL and to examine effects of cell differentiation on LpL binding. PG synthesis was examined by radiolabeling THP-1 monocytes and macrophages (a cell line originally derived from a patient with acute monocytic leukemia) with [35S]sodium sulfate and [3H]serine or [3H]glucosamine. Radiolabeled PGs isolated from the cell surface were purified by chromatography and identified as chondroitin-4-sulfate (CS) PG and heparan sulfate (HS) PG. A sixfold increase in CSPG and an 11-fold increase in HSPG accompanied cell differentiation. Whereas HS glycosaminoglycan chains from both monocytes and macrophages were 7.5 kD in size, CS chains increased in size from 17 kD to 36 kD with cell differentiation, and contained hexuronyl N-acetylgalactosamine-4,6-di-O sulfate disaccharides. LpL binding was sevenfold higher to differentiated cells, and affinity chromatography demonstrated that two cell surface PGs bound to LpL: HSPG and the oversulfated CSPG produced only by differentiated cells. We conclude that differentiation-associated changes in cell surface PG of human macrophages have functional consequences that could increase the atherogenic potential of the cells.
Edwards
I J
IJ
Wake Forest University, Department of Comparative Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1040, USA.
Xu
H
H
Obunike
J C
JC
Goldberg
I J
IJ
Wagner
W D
WD
D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011508:Chondroitin Sulfate Proteoglycans; D004187:Disaccharides; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008071:Lipoprotein Lipase; D011509:Proteoglycans