title: Maleylated-BSA induces hydrolysis of PIP2, fluxes of Ca2+, NF-kappaB binding, and transcription of the TNF-alpha gene in murine macrophages.
abstract: The interaction of altered lipids or proteins with the several scavenger receptors (SR) on macrophages can lead to disparate results in both gene expression and cell function. However, the molecular bases of signaling induced by SR ligation have remained obscure. Here we report that maleylated-bovine serum albumin (maleyl-BSA) binds a low-affinity SR, initiating PIP2 hydrolysis, [Ca2+]i spikes, phospholipase A2 (PLA2) activation, nuclear factor-kappa(B) (NF-kappa(B)) binding to its cognate nucleotide and tumor necrosis factor alpha (TNF-alpha) gene transcription. We recently reported that oxidized low-density lipoprotein (ox-LDL), which binds another macrophage SR, induced pertussis-toxin-sensitive hydrolysis of PIP2 and elevations in [Ca2+]i [J. Biol. Chem. 270, 3475-3478, 1995]. By contrast, maleyl-BSA-initiated events were not pertussis toxin-sensitive and produced less [Ca2+]i spiking than ox-LDL. Furthermore, maleyl-BSA led to binding of NF-kappa(B) to its cognate nucleotide and TNF-alpha gene transcription, whereas ox-LDL suppressed these events. Collectively, this data suggests that maleyl-BSA and ox-LDL bind to distinct SR on murine macrophages, initiate distinct signal transduction pathways, and produce different functional effects.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.forename: R E
authors.initials: RE
authors.lastname: Shackelford
authors.forename: K
authors.initials: K
authors.lastname: Florine-Casteel
authors.forename: S F
authors.initials: SF
authors.lastname: Thai
authors.forename: P B
authors.initials: PB
authors.lastname: Alford
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
authors.forename: D O
authors.initials: DO
authors.lastname: Adams
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D037342:Pertussis Toxin; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015290:Second Messenger Systems / Q000502:physiology; D012710:Serum Albumin, Bovine; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000418:Albumins; D004075:Diglycerides; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D016328:NF-kappa B; D019269:Phosphatidylinositol 4,5-Diphosphate; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D017923:Sodium-Hydrogen Exchangers; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; C049877:maleylalbumin; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D002118:Calcium