title: Comparative analysis of lipotoxicity induced by endocrine, pharmacological, and innate immune stimuli in rat basophilic leukemia cells.
abstract: Cellular lipotoxicity manifests as the steatotic accumulation of lipid droplets or lipid bodies, and/or induction of phospholipidosis. Lipotoxicity can be induced by hyperinsulinemia/nutrient overload, cationic amphiphilic drugs (CAD), and innate immunological stimuli, all of which are stimuli relevant to mast cell physiology. Hyper-accumulation of mast cell lipid bodies in response to hyperinsulinemia has been documented, but lipotoxicity in response to CAD or innate immunologic stimuli has not been analysed comparatively. Moreover, gaps in our understanding of this steatosis remain, specifically as to whether hyperinsulinemia-driven steatosis in these cells attains lipotoxic levels or is accompanied by phospholipidosis. To compare endocrine, pharmacological, and innate immunological stimuli for their ability to induce steatosis and phospholipidosis in a rat basophilic leukemia mast cell model (RBL2H3), differential fluorescence microscopy staining and quantitation of phospholipidosis and steatosis in the RBL2H3 cell line was examined. The three classes of stimuli differentially induced phospholipidosis and steatosis. PPARγ up-regulation was not uniformly associated with the expansion of the lipid body population. Fluorescence imaging of lipid-enriched structures generated in response to lipotoxic cationic amphiphilic drugs, chronic insulin exposure, and TLR2/4 ligands revealed differential staining patterns when visualized using lipophilic dyes. It is concluded that lipotoxicity-inducing pathways in this model mast cell system are diverse, and include steatotic responses to an endocrine stimulus, as well as phospholipidosis responses to cationic lipophilic drugs not previously described in this cell type.
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University , Honolulu, HI , USA .
authors.forename: Kristina
authors.initials: K
authors.lastname: Maaetoft-Udsen
authors.forename: William E
authors.initials: WE
authors.lastname: Greineisen
authors.forename: Johnny Tudela
authors.initials: JT
authors.lastname: Aldan
authors.forename: Hazelle
authors.initials: H
authors.lastname: Magaoay
authors.forename: Cheryll
authors.initials: C
authors.lastname: Ligohr
authors.forename: Lori M N
authors.initials: LM
authors.lastname: Shimoda
authors.forename: Carl
authors.initials: C
authors.lastname: Sung
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D007113:Immunity, Innate; D015471:Leukemia, Basophilic, Acute / Q000276:immunology* / Q000473:pathology; D066292:Lipid Droplets / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000276:immunology; D047495:PPAR gamma / Q000276:immunology; D010743:Phospholipids / Q000276:immunology*; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D009363:Neoplasm Proteins; D047495:PPAR gamma; D010743:Phospholipids; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Lipotoxicity; mast cells; phospholipidosis; steatosis