CYCLOSPORINE DOES NOT PREVENT CYTOPLASMIC CALCIUM CHANGES ASSOCIATED WITH LYMPHOCYTE ACTIVATION

Publisher Website
Google Scholar
Abstract
The recent development of fluorescent reagents that are sensitive to Ca ions has made it possible to quantitate cytoplasmic Ca levels of lymphocytes. The cytoplasmic Ca concentration more than doubles within the first few minutes following [mouse] lymphocyte stimulation. It is likely that this increase in Ca is an absolute requirement for mitogenic commitment. Brief exposure of T cells to concanavalin A (Con A) is sufficient to stimulate cell division, provided that extracellular Ca ions are available to the cells at the time of exposure to mitogen; no mitogenesis occurs if extracellular Ca is below 10-5 M. Commitment to mitosis requires both Con A acting at the cell surface and a source of extracellular Ca, so it follows that the plasma membrane is implicated in the control of cytoplasmic Ca changes. The lipid-soluble nature of [the immunosuppressant] cyclosporine (Cys) results in the partitioning of this drug into the plasma membrane of lymphocytes; the possibility arises that Cys might inhibit lymphocyte activation by perturbing membrane structure so as to alter regulatory fluxes in cytoplasmic Ca. Early changes in cytoplasmic Ca levels of activated T cells occur normally in the presence of Cys.