Fibronectin stimulates macrophage uptake of low density lipoprotein-heparin-collagen complexes.
In this study, we investigated whether fibronectin will enhance macrophage uptake of particulate complexes of low density lipoproteins (LDL), heparin, and fibrillar collagen and whether fibronectin's opsonic effect could be modulated by the heparin component in these model matrices. We isolated a heparin fraction (HepFn) based on its affinity to fibronectin. HepFn appeared more charged than unfractionated heparin, as evidenced by enhanced electrophoretic mobility and ability to effect a cathodic shift in the electrophoretic migration of fibronectin. HepFn lacked the smaller molecular weight species present in unfractionated heparin. Macrophage endocytosis of LDL-heparin-collagen complexes, as evidenced by the intracellular accumulation of LDL-derived cholesteryl esters and endogenously synthesized cholesteryl esters, was enhanced by fibronectin. When LDL matrix complexes were prepared with HepFn, fibronectin's opsonic properties were significantly enhanced. F(ab)2 fragments of anti-fibronectin, capable of inhibiting fibronectin's opsonization of gelatin-derivatized latex particles, inhibited the fibronectin-dependent stimulation of cholesteryl ester synthesis by macrophages exposed to LDL-HepFn-collagen complexes. Thus, fibronectin stimulates macrophage endocytosis of LDL matrix complexes. The affinity of the constituent glycosaminoglycan for fibronectin is important in the regulation of this phenomenon.
Falcone
D J
DJ
Department of Pathology, Cornell University Medical College, New York, New York.
Salisbury
B G
BG
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding; D013268:Stimulation, Chemical
D001053:Apolipoproteins; D002788:Cholesterol Esters; D005353:Fibronectins; D008077:Lipoproteins, LDL; D009895:Opsonin Proteins; D006493:Heparin; D003094:Collagen