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Internalization of Formyl Peptide Receptor in Leukocytes Subject to Fluid Stresses

机译:液体压力下白细胞中甲酰肽受体的内在化

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摘要

Human leukocytes retract pseudopods under normal physiologic levels of fluid shear stress even in the absence of any other mediator. To gain more detailed understanding of the mechanisms that regulate this cell behavior, we exposed leukocytes to a steady state laminar shear field in a flow chamber and computed the fluid stresses distribution on the surface of individual cells with and without pseudopod. The surface fluid stress distribution on such cell is quite inhomogeneous. We hypothesized that the local fluid stresses on the cell surface serve to regulate pseudopod retraction by way of membrane receptors, especially the formyl peptide receptor (FPR). Comparison of the receptor distribution and the stress distribution over the surface of the cells indicates that the membrane fluid stress alone is not directly correlated with the extent of regional pseudopod retraction, giving further support to the hypothesis that membrane receptors are involved in the mechanotransduction of leukocytes. We observed that after exposure to fluid shear the FPR was internalized to a small intracellular compartment. This internalization appears to be independent of the original location of the receptor on the surface of the cell and the FPR appears to be more derived from multiple locations on the cell, with both higher and lower fluid stresses. The evidence suggests that FPR involvement in the pseudopod-retraction process is not limited to cell surface regions with the highest fluid shear stress, but rather a more global occurrence over the majority of the cell membrane.
机译:即使在没有任何其他介质的情况下,人类白细胞在正常生理水平的液体剪切应力作用下也能使假足退缩。为了更详细地了解调节这种细胞行为的机制,我们将白细胞暴露在流动室中的稳态层流剪切场中,并计算有无假足的单个细胞表面的流体应力分布。在这种电池上的表面流体应力分布是非常不均匀的。我们假设细胞表面的局部液体压力通过膜受体,尤其是甲酰基肽受体(FPR)来调节假足的回缩。受体分布和细胞表面应力分布的比较表明,单独的膜液应力与区域假足收缩的程度没有直接关系,这进一步支持了膜受体参与白细胞机械转导的假说。 。我们观察到在暴露于流体剪切之后,FPR被内化到一个小的细胞内区室。这种内在作用似乎与受体在细胞表面的原始位置无关,并且FPR似乎更多地来自细胞上的多个位置,具有较高和较低的流体应力。有证据表明,FPR参与假足缩回过程不限于具有最高流体剪切应力的细胞表面区域,而是在大部分细胞膜上更普遍地发生。

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