A dynamic model of calcium signaling in mast cells and LTC₄ release induced by mechanical stimuli
2014
Yao, Wei | Huang, Huaxiong | Ding, Guanghong
Mast cells (MCs) play an important role in the immune system. It is known that mechanical stimuli can induce intracellular Ca²⁺ signal and release a variety of mediators, including leukotriene C₄ (LTC₄), leading to other cellular and physiological changes. In this paper, we present a mathematical model to explore signalling pathways in MCs, by including cellular mechanisms for intracellular [Formula: see text] increase and LTC₄ release in response to mechanical stimuli, thapsigargin (TG, SERCA pump inhibitor), and LTC₄ stimuli. We show that (i) mechanical stimuli activate mechano-sensitive ion channels and induce inward ion fluxes and Ca²⁺ entry which increases intracellular Ca²⁺ concentration and releases LTC₄; (ii) TG inhibits SERCA pumps, empties the internal Ca²⁺ stores, which activates Ca²⁺ release-activated Ca²⁺ channels and results in sustained intracellular Ca²⁺ increase; and (iii) LTC₄ activates receptors on MCs surface and increases intracellular Ca²⁺ concentration. Our results are consistent with experimental observations, and furthermore, they also reveal that mechanical stimuli can increase intracellular Ca²⁺ even when LTC₄ release is blocked, which suggests a feed forward loop involved in LTC₄ production. This study may facilitate our understanding of the mechanotransduction process in MCs and provide a useful modeling tool for quantitatively analyzing immune mechanisms involving MCs.
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