A dynamic model of calcium signaling in mast cells and LTC_4 release induced by mechanical stimuli  

作　　者：Wei Yao Huaxiong Huang Guanghong Ding 

机构地区：[1]Department of Mechanics and Engineering Science,Fudan University [2]Department of Mathematics and Statistics, York University

出　　处：《Chinese Science Bulletin》2014年第10期956-963,共8页

基　　金：supported by the National Natural Science Foundation of China(11202053);the Shanghai Science Foundation(12ZR1401100);the National Basic Research Program of China(2012CB518502)

摘　　要：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 Ca2t increase and LTC4release 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)LTC4activates 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 LTC4release is blocked, which suggests a feed forward loop involved in LTC4production. 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.Mast cells （MCs） play an important role in theimmune system. It is known that mechanical stimuli caninduce intracellular Ca2＋ signal and release a variety ofmediators, including leukotriene C4 （LTC4）, leading toother cellular and physiological changes. In this paper, wepresent a mathematical model to explore signalling path-ways in MCs, by including cellular mechanisms for intra-cellular Ca2＋ increase and LTC4 release in response tomechanical stimuli, thapsigargin （TG, SERCA pumpinhibitor）, and LTC4 stimuli. We show that （i） mechanicalstimuli activate mechano-sensitive ion channels and induceinward ion fluxes and Ca2＋ entry which increases intra-cellular Ca2＋ concentration and releases LTC4; （ii） TGinhibits SERCA pumps, empties the internal Ca2＋ stores,which activates Ca2＋ release-activated Ca2＋ channels andresults in sustained intracellular Ca2＋ increase; and （iii）LTC4 activates receptors on MCs surface and increasesintracellular Ca2＋ concentration. Our results are consistentwith experimental observations, and furthermore, they alsoreveal that mechanical stimuli can increase intracellularCa2＋ even when LTC4 release is blocked, which suggests afeed forward loop involved in LTC4 production. This studymay facilitate our understanding of the mechanotransduc-tion process in MCs and provide a useful modeling tool forquantitatively analyzing immune mechanisms involvingMCs.

关 键 词：CELLS CALCIUM SIGNALING LTC4 RELEASE Dynamics Mechanical stimuli 

分 类 号：Q25[生物学—细胞生物学]