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

  • Article
  • Biophysics
  • Published:
Chinese Science Bulletin

Abstract

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.

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Acknowledgement

This work was supported by the National Natural Science Foundation of China (11202053), the Shanghai Science Foundation (12ZR1401100), and the National Basic Research Program of China (2012CB518502).

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Authors and Affiliations

  1. Department of Mechanics and Engineering Science, Fudan University, Shanghai, 200433, China

    Wei Yao & Guanghong Ding

  2. Department of Mathematics and Statistics, York University, Toronto, M3J 1P3, Canada

    Huaxiong Huang

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  1. Wei Yao
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  2. Huaxiong Huang
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  3. Guanghong Ding
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Correspondence to Guanghong Ding.

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Yao, W., Huang, H. & Ding, G. A dynamic model of calcium signaling in mast cells and LTC4 release induced by mechanical stimuli. Chin. Sci. Bull. 59, 956–963 (2014). https://doi.org/10.1007/s11434-013-0110-8

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  • DOI: https://doi.org/10.1007/s11434-013-0110-8

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