Yang Zhangsheng, Nicholson Susannah E, Cancio Tomas S, Cancio Leopoldo C, Li Yansong
Combat Casualty Care Research Team (CRT) 3, United States (US) Army Institute of Surgical Research, Joint Base San Antonio (JBSA)- Fort Sam Houston, TX, United States.
Division of Trauma Research, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Front Immunol. 2023 Mar 17;14:1100461. doi: 10.3389/fimmu.2023.1100461. eCollection 2023.
The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, and there is an unmet demand for pharmacologic therapies targeting the underlying pathology of ARDS in patients suffering from the illness. The complement cascade (ComC) plays an integral role in the regulation of both innate and adaptive immune responses. ComC activation can prime an overzealous cytokine storm and tissue/organ damage. The ARDS and acute lung injury (ALI) have an established relationship with early maladaptive ComC activation. In this review, we have collected evidence from the current studies linking ALI/ARDS with ComC dysregulation, focusing on elucidating the new emerging roles of the extracellular (canonical) and intracellular (non-canonical or complosome), ComC (complementome) in ALI/ARDS pathobiology, and highlighting complementome as a vital nexus of the pathobiological connectome for ALI/ARDS its crosstalking with other systems of the immunome, DAMPome, PAMPome, coagulome, metabolome, and microbiome. We have also discussed the diagnostic/therapeutic potential and future direction of ALI/ARDS care with the ultimate goal of better defining mechanistic subtypes (endotypes and theratypes) through new methodologies in order to facilitate a more precise and effective complement-targeted therapy for treating these comorbidities. This information leads to support for a therapeutic anti-inflammatory strategy by targeting the ComC, where the arsenal of clinical-stage complement-specific drugs is available, especially for patients with ALI/ARDS due to COVID-19.
急性呼吸窘迫综合征（ARDS）病理生物学的标志是不受控制的炎症驱动的弥漫性肺泡损伤和肺泡-毛细血管屏障功能障碍。目前，ARDS的治疗干预措施在很大程度上仍局限于肺部支持策略，对于针对ARDS潜在病理的药物治疗，ARDS患者的需求尚未得到满足。补体级联反应（ComC）在先天性和适应性免疫反应的调节中起着不可或缺的作用。ComC激活可引发过度的细胞因子风暴和组织/器官损伤。ARDS和急性肺损伤（ALI）与早期不适应性ComC激活存在既定关系。在本综述中，我们收集了当前研究中有关ALI/ARDS与ComC失调相关的证据，重点阐明细胞外（经典）和细胞内（非经典或补体小体）ComC（补体组）在ALI/ARDS病理生物学中的新出现作用，并强调补体组作为ALI/ARDS病理生物学连接组的重要枢纽，及其与免疫组、损伤相关分子模式组、病原体相关分子模式组、凝血组、代谢组和微生物组等其他系统的相互作用。我们还讨论了ALI/ARDS护理的诊断/治疗潜力和未来方向，最终目标是通过新方法更好地定义机制亚型（内型和治疗型），以便促进更精确、有效的补体靶向治疗来治疗这些合并症。这些信息支持通过靶向ComC的治疗性抗炎策略，目前有临床阶段的补体特异性药物库可用，尤其是对于因COVID-19导致ALI/ARDS的患者。
