beta-VLDL and acetylated-LDL binding to pigeon monocyte macrophages.
Blood-derived monocytes are an important source of foam cells in atherosclerotic lesions of White Carneau pigeons. Based upon studies with cultured blood monocytes (monocyte macrophages) and peritoneal macrophages from a variety of mammalian species, it has been proposed that these cells become loaded with cholesteryl esters through the uptake of lipoproteins including beta-migrating very low density lipoproteins (beta-VLDL) and low density lipoproteins that have been chemically modified in a manner analogous to experimental acetylation (Ac-LDL). The purpose of this study was to determine whether similar mechanisms functioned in pigeon monocyte macrophages. Radioiodinated pigeon beta-VLDL and Ac-LDL were incubated with White Carneau pigeon monocyte macrophages that had been maintained in culture for 7 days. Scatchard analysis of the specific binding data revealed the presence of specific and saturable receptors for both beta-VLDL and Ac-LDL. beta-VLDL receptors had both low and high affinity binding components, whereas Ac-LDL receptors displayed a single class of high affinity binding sites. beta-VLDL binding remained relatively constant from 3 to 10 days in culture while Ac-LDL binding increased with time in culture. Competition studies demonstrated a high degree of binding specificity for 125I-Ac-LDL, but less for 125I-beta-VLDL. Binding of 125I-beta-VLDL was not competed for by Ac-LDL, but was by beta-VLDL and by low density lipoproteins from both normal and hypercholesterolemic pigeons. Following binding of beta-VLDL and Ac-LDL, the lipoproteins were rapidly internalized and degraded. Although the majority of degradation was secondary to internalization by the monocyte macrophages, approx. 5% of the degradation resulted from enzymatic activity in the culture medium, presumably due to secretion of proteolytic enzymes by the cells. As measured by esterification of [14C]oleate to cholesterol, it was shown that the cholesterol liberated from the degradation of both beta-VLDL and Ac-LDL stimulated cholesteryl ester synthesis in pigeon monocyte macrophages. These studies confirm the existence of specific beta-VLDL and Ac-LDL receptors on the surface of pigeon monocyte macrophages which facilitate both internalization of the lipoproteins and subsequent stimulation of cholesteryl ester synthesis. This is the first demonstration of beta-VLDL and Ac-LDL receptors on monocyte macrophages from an avian species, and the findings support the potential role for the receptor-mediated uptake of a variety of abnormal lipoproteins in the formation of monocyte-derived foam cells in the arterial wall of White Carneau pigeons during the development of atherosclerosis.
Henson
D A
DA
Department of Pathology, Wake Forest University, Winston-Salem, NC.
St Clair
R W
RW
Lewis
J C
JC
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules; D002788:Cholesterol Esters / Q000378:metabolism; D010856:Columbidae; D007700:Kinetics; D007958:Leukocyte Count; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011973:Receptors, LDL / Q000032:analysis / Q000378:metabolism*; D051116:Receptors, Scavenger; D013997:Time Factors
D015815:Cell Adhesion Molecules; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D051116:Receptors, Scavenger; C036053:VLDL receptor; C032629:acetyl-LDL; D010447:Peptide Hydrolases