Gout is an inflammatory disease triggered by deposition of monosodium urate (MSU) crystals in the joints, resulting in high neutrophil influx and pain. Here, we studied the role of the inhibitory receptor CD300a in the resolution process in a murine model of gout. We found increased CD300a expression on neutrophils emigrated to the joint. When compared to WT mice, CD300a^−/− mice had persistent neutrophil influx till 24 hr after MSU injection. This was associated with increased concentration of IL-1β and greater tissue damage in the joints of CD300a^−/− mice. There was an increase in the percentage of apoptotic neutrophils in the synovial lavage of WT mice, as compared to CD300a^−/− mice. This difference was reflected in the decline of efferocytic events in the synovial cavity of CD300a^−/− mice 24 hr after MSU injection. A CD300a agonistic antibody was shown, for the first time, to increase apoptosis of human neutrophils, and this was associated with cleavage of caspase-8. In conclusion, our results reveal an important role of CD300a in the control of leucocyte infiltration, IL-1β production and caspase-8 cleavage in neutrophils, contributing to the resolution of inflammation triggered by MSU injection.

中文翻译：

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CD300a 通过控制中性粒细胞凋亡促进由 MSU 晶体引发的关节炎症的消退

痛风是一种炎症性疾病，由尿酸单钠 (MSU) 晶体在关节中沉积引发，导致中性粒细胞大量流入和疼痛。在这里，我们研究了抑制性受体 CD300a 在痛风小鼠模型消退过程中的作用。我们发现迁移到关节的中性粒细胞上的 CD300a 表达增加。与 WT 小鼠相比，CD300a ^-/-小鼠在 MSU 注射后 24 小时内有持续的中性粒细胞流入。这与 CD300a ^-/-小鼠关节中 IL-1β 浓度增加和组织损伤更大有关。与 CD300a 相比，WT 小鼠滑膜灌洗液中凋亡中性粒细胞的百分比有所增加^-/-老鼠。这种差异反映在注射 MSU 后 24 小时CD300a ^-/-小鼠滑膜腔中的 efferocytic 事件的下降。首次显示 CD300a 激动性抗体可增加人中性粒细胞的凋亡，这与 caspase-8 的切割有关。总之，我们的研究结果揭示了 CD300a 在控制中性粒细胞中白细胞浸润、IL-1β 产生和 caspase-8 裂解中的重要作用，有助于消除由 MSU 注射引发的炎症。