Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+ ) cell signalling. Reduced TRPM3 has been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilisation has yet to be determined.
Fifteen CFS/ME patients (mean age 48.82 ± 9.83 years) and 25 health controls (mean age 39.2 ± 12.12 years) were examined.
Isolated 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 PregS, Thapsigargin, 2APB and ionomycin.
Unstimulated CD56Bright CD16Dim/- NK cells, significantly reduced TRPM3 receptors were seen in CFS/ME compared with HC. Ca2+ flux showed no significant difference between groups. Moreover PregS stimulated CD56Bright CD16Dim/- NK cells showed significant increase in Ca2+ flux in CFS/ME patients compared with HC.
By comparison, unstimulated CD56Dim CD16+ NK cell showed no significant difference in both Ca2+ flux and TRPM3 expression. PregS stimulated CD56Dim CD16+ NK cells significantly increased TRPM3 expression 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 healthy controls.
Differential expression of TRPM3 and Ca2+ flux between NK cell sub-types may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.
Calcium mobilisation in natural killer cells from Chronic fatigue syndrome/Myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels, by T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik in Clin Exp Immunol. 2016 Oct 11. [Epub ahead of print]