HUMAN CYTOMEGALOVIRUS MODULATES THE CA2-CULTURES( RESPONSE TO VASOPRESSIN AND ATP IN FIBROBLAST)

The free calcium concentrations in the nucleus ([Ca2+](n)) and in cyto sol ([Ca2+](c)) of cultured human embryonic lung (HEL) fibroblasts wer e estimated by confocal laser microscopy using the Ca2+-indicator Indo -(1). In resting HEL cells, the free cellular Ca2+-concentration signi ficantly increased upon human cytomegalovirus (HCMV) infection, The ra tio between [Ca2+](n) and [Ca2+](c) was not affected, Following stimul ation by ATP or [Arg(8)] vasopressin (AVP), a differential Ca2+ respon se of the HCMV-infected HEL cells was observed. While uninfected cells were highly sensitive to AVP and only poorly sensitive to ATP, infect ed cells showed a high responsiveness to ATP but not to AVP, This swit ch in sensitivity to the agonists was first observed at 24 h post infe ction. The Ca2+-rise following ATP or AVP stimulation was derived from intracellular Ca2+ stores. The magnitude of the ATP-induced Ca2+-rise increased upon infection, In contrast to non-infected cells where [Ca 2+](n) > [Ca2+](c) during stimulation with AVP or ATP, no nucleo-cytos olic Ca2+-gradient was observed in infected cells, Furthermore, the ma gnitude of the Ca2+ rise in the two compartments was higher in ATP-sti mulated cells. It is concluded that HCMV infection significantly Ca2+- homeostasis in HEL cells which could be related to the pathogenesis of the disease.