Cytosolic S100A8/A9 promotes Ca2+ supply at LFA-1 adhesion clusters during neutrophil recruitment

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice caused dysregulated Ca2+ signatures in activated neutrophils resulting in reduced Ca2+ availability at the formed LFA-1/F-actin clusters with defective β2 integrin outside-in signaling during post-arrest modifications. Consequently, we observed impaired cytoskeletal rearrangement, cell polarization and spreading, as well as cell protrusion formation in S100a9-/- compared to WT neutrophils, making S100a9-/- cells more susceptible to detach under flow, thereb..., , , # Data from: Cytosolic S100A8/A9 promotes Ca2+ supply at LFA-1 adhesion clusters during neutrophil recruitment This dataset includes 8 different excel files, relevant to the manuscript: \"Cytosolic S100A8/A9 promotes Ca2+ supply at LFA-1 adhesion clusters during neutrophil recruitment\". [https://doi.org/10.5061/dryad.7d7wm384t](https://doi.org/10.5061/dryad.7d7wm384t) 5 excel files are the datasets of the 5 main figures and are named: FIGURE X_data availability. 3 excel files are the datasets of the 3 supplementary figures and are named: FIGURE X-FIGURE SUPPLEMENT X_data availability. In each excel file there are different sheets, which contain the raw data of every single figure panel and are named after them (e.g. FIG 1A, FIG 3C...) ## Abbreviations ICAM-1=Intercellular Adhesion Molecule 1 PSGL1=P-selectin glycoprotein ligand-1 LFA-1=lymphocyte function-associated antigen 1 Ca2+=Calcium ion ER= endoplasmic reticulum SOCE=store-operated calcium entry ## Descriptions The Dat...S100A8/A9是多种急慢性炎症疾病中髓系细胞分泌的内源性警报素（alarmin）。尽管目前已有越来越多证据表明细胞外S100A8/A9具有促炎效应，但人们对其胞内功能仍知之甚少。本研究证实，胞质S100A8/A9在体外流动条件下的外向内信号通路（outside-in signaling）中，对中性粒细胞黏附后的修饰过程，以及体内中性粒细胞募集均不可或缺，且该功能不依赖于其细胞外作用。 机制层面，小鼠体内S100A9基因敲除会导致活化中性粒细胞的钙离子（Ca2+）信号特征紊乱，使得已形成的淋巴细胞功能相关抗原1（LFA-1，lymphocyte function-associated antigen 1）/F-肌动蛋白簇处的钙离子可利用度降低，同时在黏附后修饰过程中出现β2整合素外向内信号通路缺陷。 因此，相较于野生型（WT）中性粒细胞，S100a9基因敲除（S100a9-/-）的中性粒细胞可见细胞骨架重排、细胞极化与铺展受损，以及细胞突起形成障碍，使得S100a9-/-细胞在流体条件下更易脱落，由此…… # 数据源自：《胞质S100A8/A9在中性粒细胞募集过程中促进LFA-1黏附簇的钙离子供应》（Cytosolic S100A8/A9 promotes Ca2+ supply at LFA-1 adhesion clusters during neutrophil recruitment） 本数据集包含8个不同的Excel文件，与上述论文相关。[https://doi.org/10.5061/dryad.7d7wm384t] 其中5个文件为5张主图的数据集，命名格式为：FIGURE X_data availability。 剩余3个文件为3张补充图的数据集，命名格式为：FIGURE X-FIGURE SUPPLEMENT X_data availability。 每个Excel文件内包含多个工作表，每个工作表对应单幅图的子图原始数据，并以对应子图名称命名（例如FIG 1A、FIG 3C等）。 ## 缩写说明 ICAM-1=细胞间黏附分子1（Intercellular Adhesion Molecule 1） PSGL1=P选择素糖蛋白配体1（P-selectin glycoprotein ligand-1） LFA-1=淋巴细胞功能相关抗原1（lymphocyte function-associated antigen 1） Ca2+=钙离子（Calcium ion） ER=内质网（endoplasmic reticulum） SOCE=钙池操纵性钙内流（store-operated calcium entry） ## 描述 The Dat...