Repelled from the wound, or randomly dispersed? Reverse migration behaviour of neutrophils characterized by dynamic modelling
Repelled from the wound, or randomly dispersed? Reverse migration behaviour of neutrophils characterized by dynamic modelling
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DOI：
10.1098/rsif.2012.0542
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发表时间：
2012-12-07
影响因子：
3.9
通讯作者：
Kadirkamanathan, Visakan
中科院分区：
文献类型：
--
作者：
Holmes, Geoffrey R.;Anderson, Sean R.;Kadirkamanathan, Visakan
随着感染威胁的中和，中性粒细胞必须从炎症部位移除，以恢复正常的组织功能。最近，出现了一种新的模式，其中有活力的中性粒细胞通过一种最好描述为反向迁移的过程从炎症部位迁移。一般认为这一过程是趋化性的镜像，在趋化性线索的梯度下，中性粒细胞被吸引到感染或组织损伤区域。事实上，人们正在努力找出驱使中性粒细胞通过相反过程（逃逸）离开的线索。利用透明斑马鱼幼体中性粒细胞中表达的光转化色素，我们能够在体内对炎症溶解过程中每个中性粒细胞的位置进行成像。这些中性粒细胞坐标在动态建模框架内进行分析，使用不同形式的漂移-扩散方程以及基于近似贝叶斯计算的模型选择和参数估计。这一分析表明，实验数据最好由一个包含扩散项但没有漂移项的模型拟合，其中漂移的存在将表明趋向性。这一结果首次提供了严格的数据驱动证据，证明中性粒细胞在体内的反向迁移不是一种逃逸形式，而是一种随机再分布。
Following neutralization of infectious threats, neutrophils must be removed from inflammatory sites for normal tissue function to be restored. Recently, a new paradigm has emerged, in which viable neutrophils migrate away from inflammatory sites by a process best described as reverse migration. It has generally been assumed that this process is the mirror image of chemotaxis, where neutrophils are drawn into the areas of infection or tissue damage by gradients of chemotactic cues. Indeed, efforts are underway to identify cues that drive neutrophils away by the reverse process, fugetaxis. By using photoconvertible pigments expressed in neutrophils in transparent zebrafish larvae, we were able to image the position of each neutrophil during inflammation resolution in vivo. These neutrophil coordinates were analysed within a dynamic modelling framework, using different forms of the drift-diffusion equation with model selection and parameter estimation based on approximate Bayesian computation. This analysis revealed the experimental data were best fitted by a model incorporating a diffusion term but no drift term-where the presence of drift would indicate fugetaxis. This result, for the first time, provides rigorous data-driven evidence that reverse migration of neutrophils in vivo is not a form of fugetaxis, but rather a stochastic redistribution.