Objective Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.

Methods and Results Using flow cytometry to detect platelet activation (and release of α and dense granule contents) and the combination of Western blotting, enzyme-linked-immunosorbent assay, and immunogold labeling transmission electron and immunofluorescence microscopy, we identified that resting human platelets contain mature IL-1β. Platelets release IL-1β within minutes in response to adenosine diphosphate (ADP), collagen, and thrombin receptor agonists, but not in response to conventional NLRP3 inflammasome agonists—lipopolysaccharide and adenosine triphosphate. The rapid release of IL-1β in response to ADP and thrombin receptor agonists was independent of caspases (including caspase-1) and NLRP3. Immature and mature IL-1β were identified as low-abundance proteins on transmission electron microscopy of human platelets, and were localized to the platelet cytosol, open canalicular system, and the periphery of α granules.

Conclusion Unlike monocytes and neutrophils, human platelets are capable of rapid agonist- and time-dependent release of IL-1β by a mechanism which is independent of caspase-1 and NLRP3.

目的 血小板在介导对损伤的快速反应以及冠状动脉疾病的发展和进展方面都至关重要。几项研究表明，在长时间接触激动剂后，它们会通过经典途径（NLRP3 炎性体和 caspase-1 裂解以释放活性 IL-1β）产生和释放炎症介质，包括白细胞介素 1β (IL-1β)，如白细胞。本研究旨在确定 IL-1β 是否响应可溶性血小板激动剂快速释放，以及这种快速释放是否依赖于 NLRP3 和 caspase-1。

方法和结果 使用流式细胞术检测血小板活化（和释放 α 和致密颗粒内容物），并结合蛋白质印迹、酶联免疫吸附试验和免疫金标记透射电子和免疫荧光显微镜，我们发现静息的人血小板含有成熟的 IL- 1β。血小板响应二磷酸腺苷 (ADP)、胶原蛋白和凝血酶受体激动剂，在几分钟内释放 IL-1β，但不响应传统的 NLRP3 炎性体激动剂——脂多糖和三磷酸腺苷。响应 ADP 和凝血酶受体激动剂的 IL-1β 快速释放与半胱天冬酶（包括半胱天冬酶-1）和 NLRP3 无关。在人血小板的透射电子显微镜下，未成熟和成熟的 IL-1β 被鉴定为低丰度蛋白，

结论 与单核细胞和中性粒细胞不同，人血小板能够通过不依赖于 caspase-1 和 NLRP3 的机制快速释放 IL-1β 的激动剂和时间依赖性。