Hausburg Melissa A, Banton Kaysie L, Cassidy Christopher D, Madayag Robert M, Palacio Carlos H, Williams Jason S, Bar-Or Raphael, Ryznar Rebecca J, Bar-Or David
Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America.
Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America.
PLoS One. 2025 Jan 8;20(1):e0317056. doi: 10.1371/journal.pone.0317056. eCollection 2025.
Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g., acute appendicitis (AA), causes formation of reactive ascitic fluid (rA) that activates peritoneum surface mesothelial cells (MCs) to form adhesions. Pathologic adhesions may arise if restoration of MC-regulated fibrinolysis and secretion of glycocalyx (GCX) are disrupted. Proteins affecting these processes may originate from peritoneal rA. This is a prospective observational IRB-approved study at three Level 1 trauma centers where rA is collected prior to surgical intervention for non-perforated AA or adhesiolysis for SBO. Samples from 48 appy and 15 SBO patients were used to treat human MCs and subjected to quantification of 85 inflammatory mediators. Results were compared between patients with surgically naïve abdomens (naïve) and patients with >1 PAS. Select rA caused MCs to form clusters of fibroblastic cells, extracellular matrix fibers (FIB), and secretion of GCX. PAS and naïve patient rA fluids were clustered into "fiber-GCX" (FIB-GCX) groups: highFIB-highGCX, highFIB-lowGCX, noFIB-highGCX, noFIB-lowGCX, and noFIB-noGCX. Between groups, 26 analytes were differentially abundant including innate immune response, wound healing, and mucosal defense proteins. Factors that contributed to the differences between groups were rA-induced highFIB and history of PAS. Overall, PAS patient rA showed a muted immune response compared to rA from naïve patients. Our data suggest that abdominal surgery may negatively impact future immune responses in the abdomen. Further, quantifying immunomodulators in peritoneal rA may lead to the development a personalized approach to post-surgical adhesion treatment and prevention.
既往腹部手术（PAS）会因粘连增加小肠梗阻（SBO）的风险，而阑尾切除术（appy）是腹部粘连相关并发症的独立危险因素。腹膜炎症，如急性阑尾炎（AA），会导致反应性腹水（rA）形成，激活腹膜表面间皮细胞（MCs）形成粘连。如果MC调节的纤维蛋白溶解和糖萼（GCX）分泌的恢复受到破坏，可能会形成病理性粘连。影响这些过程的蛋白质可能源自腹膜rA。这是一项在三个一级创伤中心进行的前瞻性观察性研究，经机构审查委员会（IRB）批准，在对非穿孔性AA进行手术干预或对SBO进行粘连松解术前收集rA。来自48例阑尾切除术患者和15例SBO患者的样本用于处理人MCs，并对85种炎症介质进行定量分析。将未接受过腹部手术的患者（未手术组）与接受过1次以上PAS的患者的结果进行比较。特定的rA会使MCs形成成纤维细胞簇、细胞外基质纤维（FIB），并分泌GCX。PAS患者和未手术组患者的rA液被分为“纤维-GCX”（FIB-GCX）组：高FIB-高GCX、高FIB-低GCX、无FIB-高GCX、无FIB-低GCX和无FIB-无GCX。组间有26种分析物丰度存在差异，包括先天性免疫反应、伤口愈合和黏膜防御蛋白。导致组间差异的因素是rA诱导的高FIB和PAS病史。总体而言，与未手术组患者的rA相比，PAS患者的rA显示出免疫反应减弱。我们的数据表明，腹部手术可能会对未来腹部的免疫反应产生负面影响。此外，对腹膜rA中的免疫调节剂进行定量分析可能会促成个性化的术后粘连治疗和预防方法的开发。
