Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) are key adhesion receptors to mediate neutrophil (PMN) recruitment and intracellular calcium (Ca2+) signaling. Binding of LFA-1 and Mac-1 to their ligands is essential in triggering Ca2+ transients and activating Ca2+-dependent kinases involved in cytoskeletal remodeling and migratory function. While mechanical forces are critical in regulating integrin-mediated Ca2+ transients, it is still unclear how the bond strength of β2-integrin-ligand pair affects Ca2+ responses. Here three typical ligands with known mechanical features with LFA-1 and Mac-1 in our previous work were adopted to quantify their capabilities in inducing Ca2+ transients in adherent PMNs under shear flow. Data indicated that LFA-1 dominates Ca2+ transients in PMNs on intercellular adhesive molecule 1 (ICAM-1) and junctional adhesion molecule-A (JAM-A), while Mac-1 mediates Ca2+ transients induced by receptor for advanced glycation end products (RAGE), consistent with their corresponding bond strengths. These results link β2 integrin-ligand bond strength with Ca2+ transients in PMNs, suggesting high bond strength gives rise to strong Ca2+ response especially under physiological-like shear flow. The outcomes provide a new insight in understanding the mechanical regulatory mechanisms of PMN recruitment.

中文翻译：

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机械强度决定了由β2整联蛋白与其配体的结合触发的Ca2 +瞬变。

淋巴细胞功能相关抗原1（LFA-1）和巨噬细胞1抗原（Mac-1）是介导嗜中性粒细胞（PMN）募集和细胞内钙（Ca2 +）信号传导的关键粘附受体。LFA-1和Mac-1与其配体的结合对于触发Ca2 +瞬变和激活与细胞骨架重塑和迁移功能有关的Ca2 +依赖性激酶至关重要。尽管机械力在调节整联蛋白介导的Ca2 +瞬变中至关重要，但仍不清楚β2-整联蛋白-配体对的键合强度如何影响Ca2 +响应。在这里，我们采用了我们先前工作中具有LFA-1和Mac-1已知机械特征的三种典型配体，以量化它们在剪切流下诱导粘附PMN中Ca2 +瞬变的能力。数据表明LFA-1在细胞间粘附分子1（ICAM-1）和连接粘附分子-A（JAM-A）的PMN中占主导的Ca2 +瞬变，而Mac-1介导高级糖基化终产物（RAGE）受体诱导的Ca2 +瞬变。 ），并与其相应的粘结强度保持一致。这些结果将β2整联蛋白-配体的结合强度与PMN中的Ca2 +瞬态联系起来，表明高结合强度会引起强烈的Ca2 +响应，尤其是在类似生理剪切流的情况下。结果为了解PMN募集的机械调节机制提供了新的见解。这些结果将β2整联蛋白-配体的结合强度与PMN中的Ca2 +瞬态联系起来，表明高结合强度会引起强烈的Ca2 +响应，尤其是在类似生理剪切流的情况下。结果为了解PMN募集的机械调节机制提供了新的见解。这些结果将β2整联蛋白-配体的结合强度与PMN中的Ca2 +瞬态联系起来，表明高结合强度会引起强烈的Ca2 +响应，尤其是在类似生理剪切流的情况下。结果为了解PMN募集的机械调节机制提供了新的见解。