Chouchane Osoul, Léopold Valentine, Michels Erik H A, de Brabander Justin, van Linge Christine C A, Klarenbeek Augustinus M, Wiersinga W Joost, van 't Veer Cornelis, van der Poll Tom
Center for Experimental and Molecular Medicine, Amsterdam University Medical Center - Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Division of Infectious Diseases, Amsterdam University Medical Center - Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
ERJ Open Res. 2025 Jun 23;11(3). doi: 10.1183/23120541.00863-2024. eCollection 2025 May.
Platelets play a crucial role, amongst others, in the host response to infection through the release of proinflammatory and procoagulant proteins. Pneumonia represents a major disease burden, which has further increased since the onset of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine platelets' protein release profiles in hospitalised patients with non-COVID community-acquired pneumonia (CAP) or COVID-19.
Platelets from patients with CAP or COVID-19 and from control subjects were incubated with platelet receptor agonists stimulating either glycoprotein (GP)VI or protease-activated receptor 1 (PAR1), or medium (spontaneous release); nine platelet products were measured in supernatants. Platelet activation was also assessed by measuring P-selectin and active GPIIbIIIa surface expression by flow cytometry.
We enrolled 32 patients with CAP, 104 patients with COVID-19 and 47 control subjects. Platelets from CAP patients spontaneously released less chemokines as compared to controls, which sharply contrasted with the platelets' release profile in COVID-19, which was characterised by enhanced release of chemokines, plasminogen activator inhibitor 1 (PAI-1) and CD40 ligand relative to both controls and CAP patients. These differences were partially maintained upon stimulation of GPVI or PAR1. Enhanced GPVI-induced platelet release of P-selectin, CD40 ligand, PAI-1 and CCL5 was associated with an increased risk for the need of (non)invasive ventilation and/or mortality in COVID-19 patients. Platelet expression of P-selectin and GPIIbIIIa did not differ between groups.
Platelet release profiles differ strongly between CAP and COVID-19 patients, wherein platelets from COVID-19 patients released more bioactive products, linking with an adverse clinical outcome.
血小板在宿主对感染的反应中发挥着关键作用，其中包括通过释放促炎和促凝血蛋白来实现。肺炎是一种主要的疾病负担，自2019年冠状病毒病（COVID-19）大流行开始以来，这一负担进一步加重。我们旨在确定非COVID社区获得性肺炎（CAP）或COVID-19住院患者血小板的蛋白质释放谱。
将CAP或COVID-19患者以及对照受试者的血小板与刺激糖蛋白（GP）VI或蛋白酶激活受体1（PAR1）的血小板受体激动剂或培养基（自发释放）一起孵育；在上清液中测量九种血小板产物。还通过流式细胞术测量P-选择素和活性GPIIbIIIa表面表达来评估血小板活化。
我们纳入了32例CAP患者、104例COVID-19患者和47例对照受试者。与对照相比，CAP患者的血小板自发释放的趋化因子较少，这与COVID-19患者血小板的释放谱形成鲜明对比，后者的特征是趋化因子、纤溶酶原激活物抑制剂1（PAI-1）和CD40配体相对于对照和CAP患者均有增强释放。在刺激GPVI或PAR1后，这些差异部分得以维持。COVID-19患者中，GPVI诱导的血小板释放P-选择素、CD40配体、PAI-1和CCL5增强与需要（无创）通气和/或死亡的风险增加相关。各组之间血小板P-选择素和GPIIbIIIa的表达没有差异。
CAP和COVID-19患者的血小板释放谱差异很大，其中COVID-19患者的血小板释放更多生物活性产物，这与不良临床结局相关。
