Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2026
Trypsinogen-activated macrophage exosomes enriched in Rap1a exacerbate inflammation and predict severity in acute pancreatitis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Dai Shengjie, Wang Junru, Yi Meilin, Abdo Ebrahim, Li Haobing, Kong Hongru, Bao Liqi, Chen Geer, Sun Hongwei, Shi Keqing
Аннотация
BACKGROUND: Acute pancreatitis (AP) lacks reliable early biomarkers for predicting progression to severe acute pancreatitis (SAP). While macrophages are central to AP pathogenesis, the specific functional role of trypsinogen-activated macrophage-derived exosomes (Mφ-EXOs) remains inadequately defined. This study investigates whether these Mφ-EXOs and their cargo proteins propagate the inflammatory cascade and serve as early diagnostic assessor for AP severity.
METHODS: Macrophages were stimulated with trypsinogen in vitro, and the derived exosomes were isolated and characterized. Macrophage polarization and cytokine secretion profiles were evaluated following exosome treatment. Label-free quantitative proteomics was utilized to identify differentially expressed exosomal proteins. In vivo effects were validated using a cerulein-induced murine AP model. Clinically, plasma exosomal Rap1a levels were quantified for assessing AP severity, and diagnostic performance was assessed via receiver operating characteristic (ROC) analysis.
RESULTS: Macrophage internalization of trypsinogen induced a pro-inflammatory M1 phenotype. Trypsinogen-activated Mφ-EXOs promoted M1 polarization and enhanced IL-1β and TNF-α secretion in recipient macrophages. Proteomics identified Rap1a as significantly upregulated in these exosomes; its knockdown attenuated exosome-mediated M1 polarization. In vivo, administration of these exosomes exacerbated pancreatic and pulmonary injury. Clinically, plasma exosomal Rap1a was markedly elevated in SAP patients compared to those with non-severe AP. A predictive model combining exosomal Rap1a with serum calcium, white blood cell count, and IL-1β demonstrated high diagnostic accuracy.
CONCLUSIONS: Trypsinogen-activated macrophages contribute to systemic inflammation in AP via the release of Rap1a-enriched exosomes. Plasma exosomal Rap1a demonstrates potential clinical utility as an early, mechanistically-grounded biomarker for predicting SAP severity.
METHODS: Macrophages were stimulated with trypsinogen in vitro, and the derived exosomes were isolated and characterized. Macrophage polarization and cytokine secretion profiles were evaluated following exosome treatment. Label-free quantitative proteomics was utilized to identify differentially expressed exosomal proteins. In vivo effects were validated using a cerulein-induced murine AP model. Clinically, plasma exosomal Rap1a levels were quantified for assessing AP severity, and diagnostic performance was assessed via receiver operating characteristic (ROC) analysis.
RESULTS: Macrophage internalization of trypsinogen induced a pro-inflammatory M1 phenotype. Trypsinogen-activated Mφ-EXOs promoted M1 polarization and enhanced IL-1β and TNF-α secretion in recipient macrophages. Proteomics identified Rap1a as significantly upregulated in these exosomes; its knockdown attenuated exosome-mediated M1 polarization. In vivo, administration of these exosomes exacerbated pancreatic and pulmonary injury. Clinically, plasma exosomal Rap1a was markedly elevated in SAP patients compared to those with non-severe AP. A predictive model combining exosomal Rap1a with serum calcium, white blood cell count, and IL-1β demonstrated high diagnostic accuracy.
CONCLUSIONS: Trypsinogen-activated macrophages contribute to systemic inflammation in AP via the release of Rap1a-enriched exosomes. Plasma exosomal Rap1a demonstrates potential clinical utility as an early, mechanistically-grounded biomarker for predicting SAP severity.