DEFECTIVE TRANSMEMBRANE CALCIUM INFLUX DE MONSTRATED IN A PRIMARY IMMUNODEFICIENCY BY VIDEO-IMAGING

A rise of intracellular calcium concentration triggered by the engagem ent of various membrane receptors is a key event in the control of cel l growth. This increase involves both a release of calcium from intrac ellular stores and the opening of a transmembrane calcium conductive p athway. Using video imaging to measure intracellular calcium concentra tion in individual fura-2-loaded cells, we detected a defect in calciu m influx in lymphocytes and fibroblasts collected from patients affect ed by a rare and new form of primary immunodeficiency. In these cells, pharmacological agents such as thapsigargin or ionomycin, and the phy siological activator bradykinin, only induced transient increases in c ytoplasmic calcium level, due to the emptying of internal stores, whil e in control cells, this initial step is followed by an additional and sustained transmembrane calcium influx. The fact that calcium influx is absent in patient's fibroblasts indicates that the related deficien cy, which is clinically associated with a lack of proliferation of T l ymphocytes, also affects cells of the non-hematopoietic lineages. This study emphasizes the adequacy of single cell imaging for determining whether some forms of pathologies are associated with a disregulation of ionic fluxes, and for identifying them accurately.