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Autoimmun Rev. 2013 Oct;12(12):1136-42. doi: 10.1016/j.autrev.2013.06.018. Epub 2013 Jul 3.

The "missing link" in autoimmunity and autism: extracellular mitochondrial components secreted from activated live mast cells.

Author information

1
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, USA; Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, USA; Department of Internal Medicine, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, USA; Department of Psychiatry, Tufts University School of Medicine, Tufts Medical Center, 136 Harrison Avenue, Boston, MA, USA; Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA. Electronic address: theoharis.theoharides@tufts.edu.

Abstract

Autoimmune diseases continue to increase, but the reason(s) remain obscure and infections have not proven to be major contributors. Mast cells are tissue immune cells responsible for allergies, but have been increasingly shown to be involved in innate and acquired immunity, as well as inflammation. This involvement is possible because of their ability to release multiple mediators in response to a great variety of triggers. We recently published that activation of mast cells is accompanied by mitochondrial fission and translocation to the cell surface from where they secrete at least ATP and DNA outside the cell without cell damage. These extracellular mitochondrial components are misconstrued by the body as "innate pathogens" leading to powerful autocrine and paracrine auto-immune/auto-inflammatory responses. We also showed that mitochondrial DNA is increased in the serum of young children with autism spectrum disorders (ASD), a condition that could involve "focal brain allergy/encephalitits". Blocking the secretion of extracellular mitochondrial components could present unique possibilities for the therapy of ASD and other autoimmune diseases. Unique formulation of the flavonoid luteolin offers unique advantages.

KEYWORDS:

ATP; Autism; DNA; Inflammation; Mast cells; Mitochondria

PMID:
23831684
DOI:
10.1016/j.autrev.2013.06.018
[Indexed for MEDLINE]
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