title: Characterization of LDL and VLDL binding sites on human basophils and mast cells.
abstract: Recent data suggest that basophils and mast cells play a potential role in the processing and accumulation of plasma lipoproteins. This study investigated the interactions of 111In-low-density lipoprotein (LDL), 111In-acetyl-LDL, and 111In-very-low-density lipoprotein (VLDL) with purified primary human blood basophils, immortalized human basophils (KU812 cell line), and a human mast cell line, HMC-1. Binding sites for 111In-LDL resolved into curvilinear Scatchard plots indicating two classes of specific binding sites on primary basophils (Bmax1, 7404 sites/cell; Kd1, 1.9 nmol/L; Bmax2, 39,611 sites/cell; Kd2, 29 nmol/L), on KU812 cells (Bmax1, 8290 +/- 2690 sites/cell; Kd1, 2.4 +/- 0.6 nmol/L; Bmax2, 46,470 sites/cell; Kd2, 33.4 +/- 7.8 nmol/L), and on HMC-1 cells (Bmax1, 7840 +/- 360 sites/cell; Kd1, 1.8 +/- 0.8 nmol/L; Bmax2, 61,450 +/- 9900 sites/cell; Kd2, 28.4 +/- 9.4 nmol/L). On KU812 cells, binding of 111In-LDL was displaced by apolipoprotein (apo)-E-rich high-density lipoprotein (HDL) (IC50, 14 +/- 6 nmol/L), LDL (IC50, 29 +/- 11 nmol/L), VLDL (IC50, 55 +/- 21 nmol/L), HDL2 (IC50, 420 +/- 140 nmol/L), and heparin (IC50, 67 +/- 28 nmol/L), whereas no competition was produced by HDL, HDL3, or acetyl-LDL (IC50, > 1 mumol/L). Western blot analysis using the monoclonal antibody C7 confirmed the presence of the LDL receptor on human basophils and HMC-1 cells. 111In-acetyl-LDL binding sites (scavenger receptor) could be detected neither on human basophils nor on HMC-1 cells. 111In-VLDL bound to a single class of high-affinity binding sites on primary basophils (Bmax, 4320 sites/cell; Kd, 10 nmol/L), KU812 cells (Bmax, 4020 +/- 840 sites/cell; Kd, 8 +/- 3 nmol/L), and HMC-1 cells (Bmax, 6143 +/- 1866 sites/cell; Kd, 4 +/- 2 nmol/L). 111In-VLDL binding was displaced by VLDL > LDL > apoE-rich HDL but not by heparin (IC50 > 1 mmol/L). In the presence of prostaglandin E1, the number of 111In-LDL receptors increased by 150% (P < .05) in the high-affinity range and by 170% (P < .01) in the low-affinity range, whereas the number of 111In-VLDL binding sites remained unchanged. VLDL, LDL, HDL, and the subclasses HDL2 and HDL3 inhibited immunological histamine release by primary normal basophils (n = 3) and mast cells (n = 3). Our results provide evidence for the existence of LDL and VLDL binding sites on human basophils and HMC-1 mast cells. The exact biological and pathophysiological roles of these sites remain to be elucidated.
authors.affiliation: Department of Nuclear Medicine, University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: S R
authors.initials: SR
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Koller
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: M
authors.initials: M
authors.lastname: Leimer
authors.forename: P
authors.initials: P
authors.lastname: Angelberger
authors.forename: J
authors.initials: J
authors.lastname: Nimpf
authors.forename: W
authors.initials: W
authors.lastname: Schneider
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D001491:Basophils / Q000378:metabolism*; D002460:Cell Line; D006636:Histamine Release; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D011869:Radioligand Assay; D011973:Receptors, LDL / Q000032:analysis*
chemical_list: D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL