Ragweed pollen-mediated IgE-independent release of biogenic amines from mast cells via induction of mitochondrial dysfunction

Grzegorz Chodaczek, Attila Bacsi, Nilesh Dharajiya, Sanjiv Sur, Tapas K. Hazra, Istvan Boldogh

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Normal functions of mitochondria are required for physiological dynamics of cells, while their dysfunction contributes to development of various disorders including those of immune system. Here we demonstrate that exposure of mast cells to ragweed pollen extract increases production of H2O2 via mitochondrial respiratory complex III. These mitochondrial ROS (mtROS) enhance secretion of histamine and serotonin from mast cells, but not enzymes such as β-hexosaminidase, independently from FcεRI-generated stimuli. The release of biogenic amines is associated with inhibition of secretory granules' H+-ATPase activity, activation of PKC-δ and microtubule-dependent motility, and it is independent from intracellular free Ca2+ levels. To asses differences from IgE-mediated mast cell degranulation we show that mtROS decrease antigen-triggered β-hexosaminidase release, while they are synergistic with antigen-induced IL-4 production in sensitized cells. Taken together, these data indicate that mitochondrial dysfunction can act independently from adaptive immunity, as well as augments Th2-type responses. Pharmacological maintenance of physiological mitochondrial function could have clinical benefits in prevention and treatment of allergic diseases.

Original languageEnglish (US)
Pages (from-to)2505-2514
Number of pages10
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 2009

Keywords

  • Degranulation
  • Mast cells
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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