A novel form of cellular communication among thymic epithelial cells: intercellular calcium wave propagation

1 Laboratory on Thymus Research, Department of Immunology, Institute Oswaldo Cruz, The Oswaldo Cruz Foundation, Rio de Janeiro; 2 Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3 Department of Neuroscience, Albert Einstein College of Medicine, University of Yeshiva, Bronx, New York 10461; and 4 Necker Hospital, CNRS UMR-8603, Paris, France Submitted 6 December 2002 ; accepted in final form 27 June 2003 We here describe intercellular calcium waves as a novel form of cellular communication among thymic epithelial cells. We first characterized the mechanical induction of intercellular calcium waves in different thymic epithelial cell preparations: cortical 1-4C18 and medullary 3-10 thymic epithelial cell lines and primary cultures of thymic "nurse" cells. All thymic epithelial preparations responded with intercellular calcium wave propagation after mechanical stimulation. In general, the propagation efficacy of intercellular calcium waves in these cells was high, reaching 80-100% of the cells within a given confocal microscopic field, with a mean velocity of 6-10 µm/s and mean amplitude of 1.4- to 1.7-fold the basal calcium level. As evaluated by heptanol and suramin treatment, our results suggest the participation of both gap junctions and P2 receptors in the propagation of intercellular calcium waves in thymic nurse cells and the more prominent participation of gap junctions in thymic epithelial cell lines. Finally, in cocultures, the transmission of intercellular calcium wave was not observed between the mechanically stimulated thymic epithelial cell and adherent thymocytes, suggesting that intercellular calcium wave propagation is limited to thymic epithelial cells and does not affect the neighboring thymocytes. In conclusion, these data describe for the first time intercellular calcium waves in thymic epithelial cells and the participation of both gap junctions and P2 receptors in their propagation. gap junctions; connexin43; P2 receptors; intercellular communication Address for reprint requests and other correspondence: L. A. Alves, Laboratory on Thymus Research, Dept. of Immunology, Institute Oswaldo Cruz, The Oswaldo Cruz Foundation, Av. Brasil 4365, Manguinhos 21045-900, Rio de Janeiro, Brazil (E-mail: Alveslaa{at}ioc.fiocruz.br ).