Snekalatha, S (2014) Ion Channels in Peripheral Blood Mononuclear Cells: Effect of Culture and Ascorbic Acid. Doctoral thesis, The Tamil Nadu Dr. M.G.R. Medical University, Chennai.
|
Text
snekalatha.pdf Download (2MB) | Preview |
Abstract
Peripheral blood mononuclear cells which include lymphocytes and monocytes play important role in the adaptive and innate immune responses. Cell mediated immunity is sub served by lymphocytes and innate immunity by granulocytes, monocytes and macrophages. Ion channels on the cell membrane play significant roles during activation of these immune cells The activation of lymphocytes is dependent on function of voltage gated potassium channels, calcium activated potassium channels and calcium release activated channels (CRAC) channels. Similarly, voltage gated proton currents play a key role in the respiratory burst of phagocytic cells. The expression of these ion channels on the membrane may change when the cells are exposed to culture environment in which they may undergo differentiation. Further, the function of these ion channels can be modulated by certain drugs for therapeutic purposes. Drugs may also alter the expression of ion channels on the cell membrane Vitamins act as immunomodulants and are known to alter gene expression in immune cells. The present work involves study of the changes in two ionic currents in peripheral blood mononuclear cells during culture and the effect of vitamin C on these currents when it is present in supraphysiological concentrations in the culture environment. The proton currents in peripheral blood monocytes were characteristically similar to proton currents reported in other mammalian phagocytes in terms of their voltage dependence and gating kinetics. The currents recorded in peripheral blood monocytes were larger than those reported in THP-1 monocytes. The proton current density decreased during culture when the cells differentiated into macrophages or dendritic cells. The changes can be correlated to a certain extent to decreased NADPH oxidase in monocyte derived cells reported earlier, though a functional significance cannot be clearly stated with the experiments done in this study. CONCLUSIONS: The following conclusions can be derived from the experiments done in the present study. • The density of voltage gated proton currents decreased significantly when monocytes differentiated into macrophages and dendritic cells in culture. This can be related to the decreased respiratory burst activity in the monocyte derived cells reported previously, since NADPH oxidase activity is closely related to proton channel function. • Density of voltage gated potassium currents in lymphocytes increased during culture. The changes observed in potassium currents during culture could be associated with functional changes in lymphocytes since potassium channels play important role in lymphocyte activation. • No change was observed in potassium currents in lymphocytes and proton currents in monocytes when ascorbic acid was present in the culture medium in supraphysiological concentrations. Hence the effect of ascorbic acid on the function of these cells is probably not due to its effect on the expression of the ion channels studied. SCOPE FOR FUTURE RESEARCH: Functional implications of the observed changes in the currents recorded in PBMC s during culture could be studied by performing functional assays for lymphocyte and monocyte function. Modulation of ion channel expression by drugs that act as immunomodulants can be studied by adding them to cell cultures and the results interpreted in the light of the present observation of changes in currents during culture. CONCLUSIONS: The following conclusions can be derived from the experiments done in the present study. • The density of voltage gated proton currents decreased significantly when monocytes differentiated into macrophages and dendritic cells in culture. This can be related to the decreased respiratory burst activity in the monocyte derived cells reported previously, since NADPH oxidase activity is closely related to proton channel function. • Density of voltage gated potassium currents in lymphocytes increased during culture. The changes observed in potassium currents during culture could be associated with functional changes in lymphocytes since potassium channels play important role in lymphocyte activation. • No change was observed in potassium currents in lymphocytes and proton currents in monocytes when ascorbic acid was present in the culture medium in supraphysiological concentrations. Hence the effect of ascorbic acid on the function of these cells is probably not due to its effect on the expression of the ion channels studied. SCOPE FOR FUTURE RESEARCH: Functional implications of the observed changes in the currents recorded in PBMC s during culture could be studied by performing functional assays for lymphocyte and monocyte function. Modulation of ion channel expression by drugs that act as immunomodulants can be studied by adding them to cell cultures and the results interpreted in the light of the present observation of changes in currents during culture.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Ion Channels, Peripheral Blood Mononuclear Cells, Culture and Ascorbic Acid. |
| Subjects: | Respiratory Medicine > Physiology > Respiratory Medicine > Physiology |
| Depositing User: | Subramani R |
| Date Deposited: | 18 Jun 2017 14:44 |
| Last Modified: | 22 Sep 2022 09:57 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/107 |
Actions (login required)
 |
View Item |
