Dynamics of Calcium Signal and Leukotriene C4Release in Mast Cells Network Induced by Mechanical Stimuli and Modulated by Interstitial Fluid Flow

2015 ◽  
Vol 8 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Wei Yao ◽  
Hongwei Yang ◽  
Yabei Li ◽  
Guanghong Ding

AbstractMast 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 LTC4release 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 LTC4release; (ii) LTC4in 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 LTC4release 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).

Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. It has been proposed that indirect strain-induced flow of interstitial fluid surrounding bone cells may be the primary mediator of mechanical stimuli in-vivo [1]. Due to the practical difficulties in ascertaining whether interstitial fluid flow is indeed the primary mediator of mechanical stimuli in the in vivo environment, much of the evidence supporting this theory has been established through in vitro investigations that have observed cellular activity in response to fluid flow imposed by perfusion chambers [2]. While such in vitro experiments have identified key mechanisms involved in the mechanotransduction process, the exact mechanical stimulus being imparted to cells within a monolayer is unknown [3]. Furthermoreit is not clear whether the mechanical stimulation is comparable between different experimental systems or, more importantly, is representative of physiological loading conditions experienced by bone cells in vivo.


Author(s):  
Qiuyun Wang ◽  
Shaopeng Pei ◽  
X. Lucas Lu ◽  
Liyun Wang ◽  
Qianhong Wu

2018 ◽  
Vol 29 (16) ◽  
pp. 1927-1940 ◽  
Author(s):  
Ran Li ◽  
Jean Carlos Serrano ◽  
Hao Xing ◽  
Tara A. Lee ◽  
Hesham Azizgolshani ◽  
...  

Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment.


2012 ◽  
Vol 12 (3) ◽  
pp. 533-553 ◽  
Author(s):  
Vittorio Sansalone ◽  
Joanna Kaiser ◽  
Salah Naili ◽  
Thibault Lemaire

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