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La régulation du calcium intracellulaire et son rôle dans la signalisation des phagocytes :

Abstract : Store operated calcium entry (SOCE) is a key regulator in the activation of leukocytes. This calcium entry is regulated by SOC channels. A new inhibitor of SOCE, the BTP2 (3,5-bistrifluoromethyl pyrazole) has been identified in T lymphocytes. We therefore investigated the effect of BTP2 on calcium homeostasis and functional responses of human neutrophils. BTP2 significantly inhibited the calcium influx after stimulation with thapsigargin or fMLF. BTP2 reduced microbicidal enzyme release and superoxide anion production. On the contrary, phagocytosis, intraphagosomal radical production and bacterial killing by neutrophils were not significantly reduced. We studied TRPC mRNA expression during granulocyte differentiation; their presence changes during myelocyte differentiation. We also investigated whether these changes of gene expression are correlated with a change of BTP2 impact on store operated calcium influx. Our results suggest that differentiated HL60 cells and neutrophils are more sensitive to BTP2 than undifferentiated HL60 cells. This work suggests that BTP2 could become an important tool to characterize calcium signaling in neutrophils. Furthermore, BTP2 or related compounds could constitute a new approach to the down regulation of neutrophils in chronic inflammatory disease without compromising antibacterial host defense.
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Submitted on : Thursday, March 29, 2018 - 4:48:07 PM
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  • HAL Id : tel-01753748, version 1



Natacha Steinckwich. La régulation du calcium intracellulaire et son rôle dans la signalisation des phagocytes :. Biologie cellulaire. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN10074⟩. ⟨tel-01753748⟩



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