title: Lipid body accumulation alters calcium signaling dynamics in immune cells.
abstract: There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets.
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Greineisen
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Speck
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: Lori M N
authors.initials: LM
authors.lastname: Shimoda
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Sung
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Phan
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States.
authors.forename: Kristina
authors.initials: K
authors.lastname: Maaetoft-Udsen
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, United States.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stokes
authors.affiliation: Laboratory of Immunology and Signal Transduction, Chaminade University, Honolulu, HI, United States; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, United States. Electronic address: hturner@chaminade.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology*; D066292:Lipid Droplets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C586286:Fcgr1a protein, rat; C584440:NFATC1 protein, rat; D012333:RNA, Messenger; D017452:Receptors, IgG; D014157:Transcription Factors
keywords: Calcium signaling; Inflammation; Lipid bodies; Steatosis