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Dynamics of Calcium Signal and Leukotriene C4 Release in Mast Cells Network Induced by Mechanical Stimuli and Modulated by Interstitial Fluid Flow

  • Wei Yao (a1), Hongwei Yang (a1), Yabei Li (a1) and Guanghong Ding (a1)


Mast cells (MCs) play an important role in the immune system. Through connective tissues, mechanical stimuli activate intracellular calcium signaling pathways, induce a variety of mediators including leukotriene C4 (LTC4) release, and affect MCs’ microenvironment. This paper focuses on MCs’ intracellular calcium dynamics and LTC4 release responding to mechanical stimuli, explores signaling pathways in MCs and the effect of interstitial fluid flow on the transport of biological messengers and feedback in the MCs network. We use a mathematical model to show that (i) mechanical stimuli including shear stress induced by interstitial fluid flow can activate mechano-sensitive (MS) ion channels on MCs’ membrane and allow Ca2+ entry, which increases intracellular Ca2+ concentration and leads to LTC4 release; (ii) LTC4 in the extracellular space (ECS) acts on surface cysteinyl leukotriene receptors (LTC4R) on adjacent cells, leading to Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. An elevated intracellular Ca2+ concentration further stimulates LTC4 release and creates a positive feedback in the MCs network. The findings of this study may facilitate our understanding of the mechanotransduction process in MCs induced by mechanical stimuli, contribute to understanding of interstitial flow-related mechanobiology in MCs network, and provide a methodology for quantitatively analyzing physical treatment methods including acupuncture and massage in traditional Chinese medicine (TCM).


Corresponding author

*Corresponding author. (W. Yao), (H. W. Yang), (Y. B. Li), (G. H. Ding)


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[1]Capite, J. D. and Parekh, A. B., CRAC channels and Ca2+ signaling in mast cells, Immunolog. Rev., 231 (2009), pp. 4558.
[2]Weber, A., Knop, J. and Maurer, M., Pattern analysis of human cutaneous mast cell populations by total body surface mapping, British J. Dermatology, 148 (2003), pp. 224228.
[3]Yao, W. and Ding, G. H., Interstitial fluid flow: simulation of mechanical environment of cells in the interosseous membrane, Acta Mech. Sinica, 27 (2011), pp. 602610.
[4]Zhang, D., Ding, G. H., Shen, X. Y., Yao, W., Zhang, Z. Y., Zhang, Y. Q., Lin, J. and Gu, Q. B., Role of mast cells in acupuncture effect: a pilot study, Explore J. Sci. Heal., 4 (2008), pp. 170177.
[5]Wang, L. N., Ding, G. H., Gu, Q. B. and Schwarz, W., Single-channel properties of a stretch-sensitive chloride channel in the human mast cell line HMC-1, Euro. Biophys. J., 39 (2010), pp. 757767.
[6]Yang, W. Z., Chen, J. Y. and Zhou, L. W., Effects of shear stress on intracellular calcium change and histamine release in rat basophilic leukemia (RBL-2H3) cells, J. Environmental Pathology Oncology, 28 (2009), pp. 223230.
[7]Zhang, D., Spielmann, A., Ding, G. H. and Schwarz, W., Activation of mast-cell degranulation by different physical stimuli involves activation of the transient-receptor-potential channel TRPV2, Physiolog. Res., 61 (2012), pp. 113124.
[8]Turner, H., Del Carmen, K. A. and Stokes, A., Link between TRPV channels and mast cell function, Handb Exp. Pharmacol., 179 (2007), pp. 457471.
[9]Kuehn, H. S. and Gilfillan, A. M., G protein-coupled receptors and the modification of FcRI-mediated mast cell activation, Immunology Lett., 113 (2007), pp. 5969.
[10]Dicapite, J. L., Shirley, A., Nelson, C., Bates, G. and Parekh, A. B., Intercellular calcium wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes, FASEB J., 23 (2009), pp. 894905.
[11]Yao, W., Huang, H. and Miura, R. M., A continuum neuronal model for the instigation and propagation of cortical spreading depression, Bull. Math. Biol., 73 (2011), pp. 27732790.
[12]Bennett, M. R., Farnell, L. and Gibson, W. G., A quantitative model of purinergicjunctional transmission of calcium waves in astrocyte networks, Biophys. J., 89 (2005), pp. 22352250.
[13]Huang, H., Miura, R. M. and Yao, W., A simplified neuronal model for the instigation and propagation of cortical spreading depression, Adv. Appl. Math. Mech., 3 (2011), pp. 759773.
[14]Li, H. Y., Chen, M. and Yang, J. F., Fluid flow along venous adventitia in rabbits: is it a potential drainage system complementary to vascular circulations?, Plos. One, 7 (2012), e41395. doi: 10.1371 /journal.pone.0041395.
[15]Yao, W., Li, Y. B. and Ding, G. H., Interstitial fluid flow: the mechanical environment of cells and foundation of meridians, Evidence-Based Complementary and Alternative Medicine, (2012), Article ID 853516, 9 pages doi:10.1155/2012/853516.
[16]Boyce, J. A., Mast cells and eicosanoid mediators:a system of reciprocal paracrine and autocrine regulation, Immunol Rev., 217 (2007), pp. 168185.
[17]Yao, W., Huang, H. X. and Ding, G. H., A dynamic model of calcium signaling in mast cells and LTC4 release induced by mechanical stimuli, China Sci. Bull., 59 (2013), pp. 956963.
[18]Koch, C. and Segev, I., Methods in Neuronal Modeling: From Ions to Networks, Cambridge: MIT Press, 1998.
[19]Su, J. H., Xu, F., Lu, X. L. and Lu, T. J., Fluid flow induced calcium response in osteoblasts: mathematical modeling, J. Biomech., 44 (2011), pp. 20402046.
[20]Youma, Y. B., Hana, J., KIMA, N., Zhang, Y. H., Kim, E., Joo, H., Leem, H. C. H., Kim, S. J., Cha, K. A. and Earm, Y. E., Role of stretch-activated channels on the stretch-induced changes of rat atrial myocytes, Prog. Biophys. Molecular Biology, 90 (2006), pp. 186206.
[21]Silva, H. S., Kapela, A. and Tsoukias, N. M., A mathematical model of plasma membrane electro physiology and calcium dynamics in vascularendothelial cells, Am. J. PhysiologyCell Physiology, 293 (2007), pp. 277293.
[22]Fink, C. F., Slepchenko, B. and Loew, L. M., Determination of time-dependent inositol-1,4,5-trisphosphate concentrations during calcium release in a smooth muscle cell, Biophys. J., 77 (1999), pp. 617628.
[23]Bennett, M. R., Farnell, L. and Gibson, W. G., A quantitative model of cortical spreading depression due to purinergic and gap-junction transmission in astrocyte networks, Biophys. J., 95 (2008), pp. 56485660.
[24]Lemon, G., Gibson, W. G. and Bennett, M. R., Metabotropic receptor activation, desensitization and sequestration-I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation, J. Theor. Biol., 223 (2003), pp. 93111.
[25]Shi, X. M., Zheng, Y. F. and Liu, Z. R., A model of calcium signaling and degranulation dynamics induced by laser irradiation in mast cells, China Sci. Bull., 53 (2008), pp. 23152325.
[26]Chang, W. C., Nelson, C. and Parekh, A. B., Ca2+ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion and expression of c-fos through ERK-dependent and independent pathways in mast cells, FASEB J., 20 (2006), pp. 23812383.
[27]Chang, W. C. and Parekh, A. B., Close functional coupling between Ca2+ release-activated Ca2+ channels, arachidonic acid release, and leukotriene C4 secretion, J. Biol. Chem., 279 (2004), pp. 2999429999.
[28]Mazel, T., Raymond, R., Raymond-Stintz, M., Jett, S., Wilson, B. S. and Bridget, B., Stochastic modeling of calcium in 3D geometry, Biophys. J., 96 (2009), pp. 16911706.
[29]Chang, W. C., Capite, J. D., Nelson, C. and and Parekh, A. B., All-or-none activation of CRAC channels by agonist elicits graded responses in populations of mast cells, J. Immunol., 179 (2007), pp. 52555263.
[30]Stokes, A. J., Shimoda, L. M., Koblan-Huberson, M., Adra, C. N. and Turner, H., A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells, J. Exp. Med., 200 (2004), pp. 137147.
[31]Langevin, H. M., Churchill, D. L., Fox, J. R., Badger, G. J., Garra, B. S. and Krag, M. H., Biomechanical response to acupuncture needling in humans, J. Appl. Physiol., 91 (2001), pp. 24712478.
[32]Yu, X. J., Ding, G. H., Huang, H., Lin, J., Yao, W. and Zhan, R., Role of collagen fibers in acupuncture analgesia therapy on rats, Connective Tissue Research, 50 (2009), pp. 110120.


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Dynamics of Calcium Signal and Leukotriene C4 Release in Mast Cells Network Induced by Mechanical Stimuli and Modulated by Interstitial Fluid Flow

  • Wei Yao (a1), Hongwei Yang (a1), Yabei Li (a1) and Guanghong Ding (a1)


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