Metabolic Consequences of IgE- and Non-IgE-Mediated Mast Cell Degranulation

被引:14
|
作者
Mendoza, Ryan P. [1 ]
Anderson, Colin C. [1 ]
Fudge, Dylan H. [1 ]
Roede, James R. [1 ]
Brown, Jared M. [1 ]
机构
[1] Univ Colorado, Dept Pharmaceut Sci, Skaggs Sch Pharm & Pharmaceut Sci, Anschutz Med Campus, Aurora, CO 80045 USA
来源
JOURNAL OF IMMUNOLOGY | 2021年 / 207卷 / 11期
基金
美国国家卫生研究院;
关键词
HISTAMINE-RELEASE; ADENOSINE-TRIPHOSPHATE; AEROBIC GLYCOLYSIS; ACTIVATION; NECROSIS; ANTIGEN; MICE;
D O I
10.4049/jimmunol.2001278
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mast cells are important effector cells in the immune system and undergo activation (i.e., degranulation) by two major mechanisms: IgE-mediated and non-IgE-mediated mechanisms. Although IgE-mediated degranulation is well researched, the cellular mechanisms of non-IgE-mediated mast cell activation are poorly understood despite the potential to induce similar pathophysiological effects. To better understand non-IgE mast cell degranulation, we characterized and compared cellular metabolic shifts across several mechanisms of degranulation (allergen-induced [IgE-mediated], 20 nm of silver nanoparticle-mediated [non-IgE], and compound 48/80-mediated [non-IgE]) in murine bone marrow-derived mast cells. All treatments differentially impacted mitochondrial activity and glucose uptake, suggesting diverging metabolic pathways between IgE- and non-IgE-mediated degranulation. Non-IgE treatments depleted mast cells' glycolytic reserve, and compound 48/80 further inhibited the ability to maximize mitochondrial respiration. This cellular reprogramming may be indicative of a stress response with non-IgE treatments. Neither of these outcomes occurred with IgE-mediated degranulation, hinting at a separate programmed response. Fuel flexibility between the three primary mitochondrial nutrient sources was also eliminated in activated cells and this was most significant in non-IgE-mediated degranulation. Lastly, metabolomics analysis of bone marrow-derived mast cells following degranulation was used to compare general metabolite profiles related to energetic pathways. IgE-mediated degranulation upregulated metabolite concentrations for the TCA cycle and glycolysis compared with other treatments. In conclusion, mast cell metabolism varies significantly between IgE- and non-IgE-mediated degranulation suggesting novel cell regulatory mechanisms are potentially driving unexplored pathways of mast cell degranulation.
引用
收藏
页码:2637 / 2648
页数:13
相关论文
共 50 条
  • [1] Cannabidiol Inhibits IgE-Mediated Mast Cell Degranulation and Anaphylaxis in Mice
    Yang, Xiaohui
    Lee, Dohyeon
    Kim, Hyun-Woo
    Park, Byung-Hyun
    Lim, Changjin
    Bae, Eun Ju
    MOLECULAR NUTRITION & FOOD RESEARCH, 2024, 68 (03)
  • [2] Non-IgE mediated mast cell activation
    Redegeld, Frank A.
    Yu, Yingxin
    Kumari, Sangeeta
    Charles, Nicolas
    Blank, Ulrich
    IMMUNOLOGICAL REVIEWS, 2018, 282 (01) : 87 - 113
  • [3] SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
    Pettersson, Hanna
    Zarnegar, Behdad
    Westin, Annika
    Persson, Viktor
    Peuckert, Christiane
    Jonsson, Jorgen
    Hallgren, Jenny
    Kullander, Klas
    SCIENTIFIC REPORTS, 2017, 7
  • [4] Inorganic arsenite inhibits IgE receptor-mediated degranulation of mast cells
    Hutchinson, Lee M.
    Trinh, Benett M.
    Palmer, Rachel K.
    Preziosi, Christopher A.
    Pelletier, Jonathan H.
    Nelson, Hannah M.
    Gosse, Julie A.
    JOURNAL OF APPLIED TOXICOLOGY, 2011, 31 (03) : 231 - 241
  • [5] The antipsychotic drug pimozide inhibits IgE-mediated mast cell degranulation and migration
    Hou, Yi-Bo
    Zhang, Li-Na
    Wang, Hui-Na
    Zhao, Zhen-Fu
    Sun, Yue-Tong
    Ji, Kunmei
    Chen, Jia-Jie
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2020, 84
  • [6] Small Interfering RNA Screen for Phosphatases Involved in IgE-Mediated Mast Cell Degranulation
    Zhang, Juan
    Mendoza, Mary
    Guiraldelli, Michel F.
    Barbu, Emilia Alina
    Siraganian, Reuben P.
    JOURNAL OF IMMUNOLOGY, 2010, 184 (12): : 7178 - 7185
  • [7] IgE Receptor-Mediated Mast-Cell Renin Release
    Aldi, Silvia
    Robador, Pablo A.
    Tomita, Kengo
    Di Lorenzo, Annarita
    Levi, Roberto
    AMERICAN JOURNAL OF PATHOLOGY, 2014, 184 (02): : 376 - 381
  • [8] An optimized method for IgE-mediated degranulation of human lung mast cells
    Gong, Yitao
    Johnsson, Anna-Karin
    Safholm, Jesper
    Al-Ameri, Mamdoh
    Sachs, Erik
    Vali, Kasra
    Nilsson, Gunnar
    Ronnberg, Elin
    FRONTIERS IN IMMUNOLOGY, 2024, 15
  • [9] Resveratrol Inhibits IgE-Mediated Basophilic Mast Cell Degranulation and Passive Cutaneous Anaphylaxis in Mice
    Han, Seon-Young
    Bae, Ji-Young
    Park, Sin-Hye
    Kim, Yun-Ho
    Park, Jung Han Yoon
    Kang, Young-Hee
    JOURNAL OF NUTRITION, 2013, 143 (05): : 632 - 639
  • [10] The Tetraspanin CD63 Is Required for Efficient IgE-Mediated Mast Cell Degranulation and Anaphylaxis
    Kraft, Stefan
    Jouvin, Marie-Helene
    Kulkarni, Nitin
    Kissing, Sandra
    Morgan, Ellen S.
    Dvorak, Ann M.
    Schroeder, Bernd
    Saftig, Paul
    Kinet, Jean-Pierre
    JOURNAL OF IMMUNOLOGY, 2013, 191 (06): : 2871 - 2878