Calcium influx kinetics, and the features of potassium channels of peripheral lymphocytes in primary Sjögren’s syndrome

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• 作者：Nó ; ra Legá ; ny^a ; Gergely Toldi^b ; Csaba Orbá ; n^c ; Nó ; ra Megyes^a ; Anna Bajnok^b ; Attila Balog^a ; ^{balog.attila@med.u-szeged.hu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AUC ; area under the curve ; [Ca2+]cyt ; cytoplasmic free calcium level ; CRAC ; calcium release activated calcium ; Max ; maximum value ; MGTX ; margatoxin ; PBMC ; peripheral blood mononuclear cell ; PHA ; phytohemagglutinin ; pSS ; primary Sjö ; gren&rsquo ; s syndrome ; RA ; rheumatoid arthritis ; TCM ; central memory T cell ; TEM ; effector memory T cell ; Th ; T helper ; tmax ; time to reach maximum value ; TRAM ; triarylmethane
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：221
• 期：11
• 页码：1266-1272
• 全文大小：760 K

文摘

The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx and present a possible target for selective immunomodulation.

Design

Case–control study.

Subjects and methods

We took peripheral blood samples from 8 healthy individuals and 15 primary Sjögren’s syndrome (pSS) patients. We evaluated calcium influx kinetics following activation in peripheral T lymphocytes. We also assessed the sensitivity of T lymphocytes to specific inhibition of the Kv1.3 and IKCa1 potassium channels, and the Kv1.3 channel expression.

Results

The basal cytoplasmatic calcium levels were lower in both Th1 and Th2 lymphocytes in pSS compared to controls. The peak of calcium influx in lymphocytes isolated from pSS patients is reached later, indicating that they respond more slowly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. In the pSS group, neither of the inhibitors induced alteration in calcium influx. Expression of Kv1.3 channels on CD4, Th2 and CD8 lymphocytes in pSS was significantly higher compared to controls.

Conclusion

The altered expression and specific inhibition of potassium channels seem to be related to altered calcium influx kinetics in pSS which distinguish pSS either from healthy controls or other systemic autoimmune diseases.