Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
J Surg Res. 2019 Mar;235:288-297. doi: 10.1016/j.jss.2018.09.028. Epub 2018 Nov 2.
Pancreas transplantation restores insulin secretion in type 1 diabetes mellitus. The graft also produces exocrine secretions that can be drained enterically (enteric drainage [ED]) or via the bladder (bladder drainage [BD]). We suggest that in BD transplants, such secretions destroy bladder innate immunity, specifically host defense peptides/proteins (HDPs), which increases patient susceptibility to recurrent urinary tract infections (rUTIs).
BD and ED patient records were reviewed retrospectively for UTIs. Urine samples from ED and BD transplant recipients were analyzed for pH, the HDPs β-defensin 2 (HBD2) and lipocalin-2, and amylase concentrations. In vitro, bacterial growth curves and antimicrobial assays were used to evaluate the effects of pH, HBD2, and HBD2 + pancreatic digestive enzymes (pancreatin) on uropathogenic Escherichia coli (UPEC) survival and growth.
Urinalysis revealed a significant difference in pH between the BD and ED cohorts (7.2 ± 0.8 versus 6.7 ± 0.8; P = 0.012). Urinary HDPs were measured and BD, but not ED, lipocalin-2 concentrations were significantly decreased compared with those of diabetics awaiting transplant (P < 0.05). In vitro, an alkaline environment, pH 8.0, concomitant with the urine of the patient who underwent BD transplantation, significantly reduced UPEC growth (P < 0.05); addition of pancreatin to the growth medium was associated with a significant increase (P < 0.001) in growth rate. Antimicrobial data suggested significant UPEC killing in the presence of HBD2 (P < 0.01), but not in the presence of HBD2 + pancreatin (>12,500 amylase units).
These in vivo and in vitro data suggest that BD pancreatic exocrine secretions inactivate the bladder innate defenses, which facilitate UPEC growth and underpins the increased susceptibility of patients who underwent BD pancreas transplantation to rUTIs.
胰腺移植可恢复 1 型糖尿病患者的胰岛素分泌。移植物还会产生外分泌分泌物，可以通过肠道（肠道引流[ED]）或通过膀胱（膀胱引流[BD]）排出。我们认为，在 BD 移植中，这些分泌物会破坏膀胱固有免疫，特别是宿主防御肽/蛋白（HDPs），从而增加患者复发性尿路感染（rUTI）的易感性。
回顾性审查 BD 和 ED 患者的尿路感染记录。分析 ED 和 BD 移植受者的尿液样本，检测 pH 值、HDPs β-防御素 2（HBD2）和脂联素-2 以及淀粉酶浓度。在体外，使用细菌生长曲线和抗菌测定来评估 pH 值、HBD2 和 HBD2+胰腺消化酶（胰酶）对尿路致病性大肠杆菌（UPEC）存活和生长的影响。
尿液分析显示 BD 和 ED 队列之间的 pH 值存在显著差异（7.2±0.8 与 6.7±0.8；P=0.012）。测量尿液中的 HDPs 发现，BD 而不是 ED 组的脂联素-2 浓度与等待移植的糖尿病患者相比显著降低（P<0.05）。在体外，碱性环境 pH8.0 与接受 BD 移植的患者尿液共同作用，显著降低 UPEC 生长（P<0.05）；在生长培养基中添加胰酶与生长速率显著增加（P<0.001）相关。抗菌数据表明，在存在 HBD2 的情况下，显著杀死 UPEC（P<0.01），但在存在 HBD2+胰酶的情况下（>12500 个淀粉酶单位）则不然。
这些体内和体外数据表明，BD 胰腺外分泌分泌物使膀胱固有防御功能失活，从而促进 UPEC 的生长，并解释了接受 BD 胰腺移植的患者易发生复发性尿路感染的原因。
