The Journal of Immunology, Vol 139, Issue 3 881-886, Copyright © 1987 by American Association of Immunologists

ARTICLES

The control of mediator release from RBL-2H3 cells: roles for Ca2+, Na+, and protein kinase C1

RF Stump, JM Oliver, EJ Cragoe Jr and GG Deanin

Antigen-stimulated rat basophilic leukemia (RBL-2H3) cells release serotonin and other inflammatory mediators by a process that requires Ca2+ influx and increased cytoplasmic Ca2+ levels, and is mimicked by Ca2+ ionophores. We report here that the Ca2+ response to antigen and to ionomycin has two components, a Ca2+ spike and a Ca2+ plateau. In nominally Ca2+-free medium, both components of the Ca2+ response are inhibited and secretion does not occur. In Na+-free medium, the initial Ca2+ spike induced by antigen or ionomycin occurs, but the plateau is again absent and secretion is inhibited by 30 to 50%. Secretion is also reduced by 10(-4) M amiloride, an inhibitor of Na+ transport pathways, and by 10(-5) M concentrations of two amiloride analogs with greater activity than amiloride, respectively, against Na+ channels and Na+/Ca2+ exchange. Phorbol esters, which stimulate protein kinase C, enhance the Ca2+ plateau and secretion caused by suboptimal amounts of both antigen and ionomycin; this enhancement depends on extracellular Na+. The Na+ ionophore, monensin, mimics the Ca2+ plateau. From these data, we infer that the Ca2+ spike and plateau reflect separate responses of RBL-2H3 cells to antigen or ionomycin. We propose that the Ca2+ plateau results at least in part from the activation of a Na+- dependent Ca2+ influx pathway. One possible mechanism is that antigen binding stimulates a protein kinase C-regulated Na+ transport system. The resulting influx of Na+ may activate a Na+/Ca2+ antiporter that supports the Ca2+ plateau and mediator release.

This article has been cited by other articles:

				H. Vincent-Schneider, P. Stumptner-Cuvelette, D. Lankar, S. Pain, G. Raposo, P. Benaroch, and C. Bonnerot Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells Int. Immunol., July 1, 2002; 14(7): 713 - 722. [Abstract] [Full Text] [PDF]

				H Vincent-Schneider, C Thery, D Mazzeo, D Tenza, G Raposo, and C Bonnerot Secretory granules of mast cells accumulate mature and immature MHC class II molecules J. Cell Sci., January 1, 2001; 114(2): 323 - 334. [Abstract] [PDF]

				B. S. Wilson, J. R. Pfeiffer, A. J. Smith, J. M. Oliver, J. A. Oberdorf, and R. J.H. Wojcikiewicz Calcium-dependent Clustering of Inositol 1,4,5-Trisphosphate Receptors Mol. Biol. Cell, June 1, 1998; 9(6): 1465 - 1478. [Abstract] [Full Text]

				B. S. Wilson, N. Kapp, R. J. Lee, J. R. Pfeiffer, A. M. Martinez, Y. Platt, F. Letourneur, and J. M. Oliver Distinct Functions of the Fc[IMAGE]R1 [IMAGE] and beta Subunits in the Control of Fc[IMAGE]R1-mediated Tyrosine Kinase Activation and Signaling Responses in RBL-2H3 Mast Cells J. Biol. Chem., February 24, 1995; 270(8): 4013 - 4022. [Abstract] [Full Text] [PDF]

				T Meyer, D Holowka, and L Stryer Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate Science, April 29, 1988; 240(4852): 653 - 656. [Abstract] [PDF]