A dynamic model of calcium signaling in mast cells and LTC4 release induced by mechanical stimuli

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 $\hbox{Ca}^{2+}$ 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.