Spontaneous calcium oscillations have been observed in a number of excitable and non-excitable cells, but in most cases their biological role remains elusive. In the present study we demonstrate that spontaneous calcium oscillations occur in immature human monocyte-derived dendritic cells, but not in dendritic cells stimulated to undergo maturation with LPS or other toll like-receptor agonists. We investigated the mechanism and role of spontaneous calcium oscillations in immature dendritic cells and found that they are mediated by the inositol-1,4,5-trisphosphate receptor since they were blocked by pre-treatment of cells with the inositol-1,4,5-trisphosphate receptor antagonist Xestospongin C and 2-APB. A component of the calcium signal is also due to influx from the extracellular environment and may be involved in maintaining the level of the intracellular calcium stores. As to their biological role, our results indicate that they are intimately linked to the immature phenotype and are associated with the translocation of the transcription factor NFAT into the nucleus. In fact, once the calcium oscillations are blocked with 2-APB or by treating the cells with LPS, NFAT remains cytoplasmic. The results presented in this report provide novel insights into the physiology of monocyte derived dendritic cells and into the mechanisms involved in maintaining the cells in the immature stage
Frequent calcium oscillations lead to NFAT activation in human immature dendritic cells.
ZORZATO, Francesco;TREVES, Susan Nella
2010
Abstract
Spontaneous calcium oscillations have been observed in a number of excitable and non-excitable cells, but in most cases their biological role remains elusive. In the present study we demonstrate that spontaneous calcium oscillations occur in immature human monocyte-derived dendritic cells, but not in dendritic cells stimulated to undergo maturation with LPS or other toll like-receptor agonists. We investigated the mechanism and role of spontaneous calcium oscillations in immature dendritic cells and found that they are mediated by the inositol-1,4,5-trisphosphate receptor since they were blocked by pre-treatment of cells with the inositol-1,4,5-trisphosphate receptor antagonist Xestospongin C and 2-APB. A component of the calcium signal is also due to influx from the extracellular environment and may be involved in maintaining the level of the intracellular calcium stores. As to their biological role, our results indicate that they are intimately linked to the immature phenotype and are associated with the translocation of the transcription factor NFAT into the nucleus. In fact, once the calcium oscillations are blocked with 2-APB or by treating the cells with LPS, NFAT remains cytoplasmic. The results presented in this report provide novel insights into the physiology of monocyte derived dendritic cells and into the mechanisms involved in maintaining the cells in the immature stageI documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
