S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Pontifícia Universidade Católica Dom Bosco, Campo Grande, MS, 79117900, Brazil.
S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Pontifícia Universidade Católica Dom Bosco, Campo Grande, MS, 79117900, Brazil; Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Pontifícia Universidade Católica de Brasília, Brasília, DF, 70790160, Brazil.
Pulm Pharmacol Ther. 2024 Sep;86:102316. doi: 10.1016/j.pupt.2024.102316. Epub 2024 Jul 26.
Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Streptococcus pneumoniae, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.
急性肺损伤(ALI)是一种严重的临床挑战,与高发病率和死亡率相关。在全球范围内,每年约有 20 万人受到影响,住院患者的死亡率高达 40%,且出院后仍存在持续的并发症。本综述重点关注细菌性 ALI 的关键免疫学途径,并探讨了作为其诱导工具的小鼠模型。这些模型是揭示 ALI 固有炎症级联和生物学反应的不可或缺的平台,同时也有助于评估新型治疗药物。然而,它们的应用并非没有挑战,主要是因为不同细菌毒力谱需要严格的生物安全协议。目前已经有简单且可重复的肺部细菌感染模型,包括气管内、鼻内、胸膜内和腹腔内途径。这些模型使用内毒素,如市售的脂多糖(LPS)或活病原体,如铜绿假单胞菌、结核分枝杆菌和肺炎链球菌,它们都与 ALI 的发病机制有关。将细菌性肺部感染的小鼠模型与对潜在免疫学机制的深入研究相结合,是推进急性细菌性肺损伤治疗领域的基石。