Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK; These authors contributed equally.
University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92093, USA; These authors contributed equally.
Trends Immunol. 2019 Jun;40(6):472-481. doi: 10.1016/j.it.2019.03.009. Epub 2019 Apr 18.
Recruitment of immune cells from the vasculature relies on the presentation of glycosaminoglycan-bound chemokines on the luminal side of vascular endothelial cells. However, the current model of chemokine-glycosaminoglycan interactions, and its implications for receptor interactions, remains poorly developed. We propose a refined 'Chemokine Cloud' model, arguing that chemokines are not presented to leukocytes bound to glycosaminoglycans, but rather, in solution while sequestered within the hydrated glycocalyx. We posit that glycosaminoglycans provide an immobilized chemokine depot maintaining a 'cloud' of 'solution-phase' chemokines within the glycocalyx, and that it is this soluble form of any given chemokine that interacts with leukocyte-bound receptors. Our proposition clarifies certain anomalies associated with the current model of chemokine-glycosaminoglycan interactions, with implications for the design of blockers of chemokine function.
免疫细胞从血管中募集依赖于血管内皮细胞管腔侧糖胺聚糖结合趋化因子的呈现。然而，趋化因子-糖胺聚糖相互作用的当前模型及其对受体相互作用的影响仍未得到充分发展。我们提出了一个改进的“趋化因子云”模型，认为趋化因子不是与糖胺聚糖结合的白细胞呈现，而是在水合糖萼内被隔离的溶液中呈现。我们假设糖胺聚糖提供了一个固定的趋化因子储存库，在糖萼内维持“云状”的“溶液相”趋化因子，并且正是这种给定趋化因子的可溶性形式与白细胞结合的受体相互作用。我们的假设澄清了与趋化因子-糖胺聚糖相互作用的当前模型相关的某些异常，这对趋化因子功能阻断剂的设计具有重要意义。
