Article ; Online: Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients.
2016 Volume 49, Issue 1, Page(s) 27
Abstract: ... NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 ... genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome ... of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed ...
| Abstract | Background: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19(+) B cells, CD56(bright) and CD56(dim) cell populations from CFS/ME patients. Results: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56(bright) TRPM3 35.72 % ± 7.37; CD56(dim) 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19(+) B cells (1.56 ± 0.191) and CD56(bright) NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19(+) B lymphocytes. CD56(bright) NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients. Conclusions: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME. |
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| MeSH term(s) | Analysis of Variance ; B-Lymphocytes/metabolism ; Calcium Channels/blood ; Case-Control Studies ; Enzyme Inhibitors/therapeutic use ; Fatigue Syndrome, Chronic/blood ; Fatigue Syndrome, Chronic/drug therapy ; Female ; Flow Cytometry/methods ; Humans ; Immunophenotyping/methods ; Killer Cells, Natural/metabolism ; Male ; Middle Aged ; Reference Values ; TRPM Cation Channels/metabolism ; Thapsigargin/therapeutic use |
| Chemical Substances | Calcium Channels ; Enzyme Inhibitors ; TRPM Cation Channels ; TRPM3 protein, human ; Thapsigargin (67526-95-8) |
| Language | English |
| Publishing date | 2016-05-31 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1138990-4 |
| ISSN | 0717-6287 ; 0716-9760 |
| ISSN (online) | 0717-6287 |
| ISSN | 0716-9760 |
| DOI | 10.1186/s40659-016-0087-2 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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