Identification of apolipoproteins involved in the interaction of human high density lipoprotein3 with receptors on cultured cells.
Human high density lipoprotein (HDL), devoid of apolipoproteins E or B, binds with high affinity and specificity to cultured cells derived from several tissues. In order to investigate the ligand specificity of the putative receptor, we have performed competitive inhibition studies to identify the components of high density lipoprotein that bind to cell surfaces of rat adrenal cortical cells and human skin fibroblasts. Radiolabeled HDL3 was displaced with unlabeled apolipoprotein-dimyristoylphosphatidylcholine recombinant particles containing AI, AII, CIII-1, and E apolipoproteins, but not by dimyristoylphosphatidylcholine complexed to albumin or by low density lipoprotein. Because exchange may readily occur between apolipoproteins in HDL and in recombinants this observation may not be truly representative of ligand competition. Further experiments using Fab fragments prepared from pure IgG to each apolipoprotein showed that binding of radioiodinated HDL to cells was suppressed following preincubation of HDL with Fab fragments raised against apolipoproteins AI or AII but not against apolipoproteins E or CIII-1 or albumin. In additional studies with apolipoprotein recombinants specific saturable binding was demonstrated between apo-AI or -AII recombinants and adrenocortical cells whereas binding of apo-CIII-2 was characterized by a large nonsaturable component which almost equaled the specific binding. The data, therefore, provide evidence for the involvement of the two major apolipoproteins (AI and AII) in HDL recognition by cellular receptors.
Fidge
N H
NH
Nestel
P J
PJ
D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000378:metabolism*; D001054:Apolipoproteins A / Q000378:metabolism; D001056:Apolipoproteins C / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001667:Binding, Competitive; D002352:Carrier Proteins; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053440:Lipoproteins, HDL3; D008854:Microscopy, Electron; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D013997:Time Factors
D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002352:Carrier Proteins; D007140:Immunoglobulin Fab Fragments; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein