Abstract |
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+ ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56dim CD16+ NK cells and CD56bright CD16dim/- NK cells. Ca2+ flux and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2-aminoethoxydiphenyl borate ( 2APB) and ionomycin. Unstimulated CD56bright CD16dim/- NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). Ca2+ flux showed no significant difference between groups. Moreover, PregS-stimulated CD56bright CD16dim/- NK cells showed a significant increase in Ca2+ flux in CFS/ME patients compared with HC. By comparison, unstimulated CD56dim CD16+ NK cells showed no significant difference in both Ca2+ flux and TRPM3 expression. PregS-stimulated CD56dim CD16+ NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca2+ flux. Furthermore, TG-stimulated CD56dim CD16+ NK cells increased K562 cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca2+ flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.
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Authors | T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik |
Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 187
Issue 2
Pg. 284-293
(Feb 2017)
ISSN: 1365-2249 [Electronic] England |
PMID | 27727448
(Publication Type: Journal Article)
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Copyright | © 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology. |
Chemical References |
- CD56 Antigen
- Receptors, IgG
- TRPM Cation Channels
- TRPM3 protein, human
- pregnenolone sulfate
- Thapsigargin
- Pregnenolone
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Topics |
- Adult
- CD56 Antigen
(metabolism)
- Calcium Signaling
- Cytotoxicity, Immunologic
- Fatigue Syndrome, Chronic
(genetics)
- Female
- Humans
- K562 Cells
- Killer Cells, Natural
(physiology)
- Male
- Middle Aged
- Pregnenolone
(metabolism)
- Receptors, IgG
(metabolism)
- TRPM Cation Channels
(genetics)
- Thapsigargin
(metabolism)
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