The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates.
The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates.
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DOI：
10.1016/j.biomaterials.2013.08.021
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发表时间：
2013-12
期刊：
影响因子：
14
通讯作者：
Keselowsky, Benjamin G.
中科院分区：
文献类型：
--
作者：
Lewis, Jamal S.;Dolgova, Natalia V.;Chancellor, Thomas J.;Acharya, Abhinav P.;Karpiak, Jerome V.;Lele, Tanmay P.;Keselowsky, Benjamin G.
树突状细胞(DC)是耐受和免疫的关键调节细胞，存在于机械活动的组织中，如动脉壁内层，由于脉动的血流，这些组织经历周期性的放射壁应变。尽管在活体实验中很难确定，但假设DC在这种机械活动的组织中经历了机械力是合理的。然而，目前尚不清楚树突状细胞对循环机械应变的反应。为了探讨DC对机械应变有反应的假设，在体外将DC培养在预先吸附的黏附蛋白(如层粘连蛋白、胶原、纤维蛋白原)上，并施加不同持续时间和应变幅度的1 Hz循环应变。与无应变对照相比，10%的应变幅度和24小时的持续时间对DC活性有不利影响，但在某些粘附性底物上培养在这种严酷的应变制度下提供了适度的活性保护。相比之下，施加1h的1 Hz循环3%应变并不影响DC的活性，并将该应变状态用于剩余的实验以量化DC激活和T细胞启动能力。应用3%的菌株可增加刺激分子(MHC-II)和共刺激分子(CD86、CD40)的表达，而在预涂胶基上培养，这种作用一般都会增强。有趣的是，树突状细胞的细胞因子分泌谱不受菌株的显著影响。最后，树突状细胞以一种独立于黏附底物的方式表现出对同种异体T细胞增殖的刺激作用。这些观察表明，DC的产生与已被描述为半成熟表型的DC一致。这项工作开始阐明树突状细胞在暴露于循环机械力的组织环境中的潜在作用。
Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine in vivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured in vitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1 Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24 h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1 h of 1 Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and co-stimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.
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影响因子：
10.8
作者：
Bobryshev, YV;Lord, RSA
通讯作者：
Lord, RSA
DOI：
10.1084/jem.187.4.579
发表时间：
1998-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Levkau B;Herren B;Koyama H;Ross R;Raines EW
通讯作者：
Raines EW
影响因子：
9.7
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
14
作者：
Acharya, Abhinav P.;Clare-Salzler, Michael J.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.