Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02 Malmö, Sweden.
Inflamm Res. 2011 Dec;60(12):1093-8. doi: 10.1007/s00011-011-0370-1. Epub 2011 Aug 24.
Neutrophil infiltration is a key regulator in the pathophysiology of acute pancreatitis (AP), although the impact of Toll-like receptors (TLRs) in AP remains elusive. The aim of this study was to define the role of TLR2 and TLR4 in leukocyte recruitment and tissue damage in severe AP.
AP was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in wild-type, TLR2- and TLR4-deficient mice. Samples were collected 24 h after induction of AP.
Taurocholate challenge caused a clear-cut pancreatic damage characterized by increased acinar cell necrosis, neutrophil infiltration, focal hemorrhage and edema formation, as well as increased levels of blood amylase and CXCL2 (macrophage inflammatory protein-2) in the pancreas and serum. Moreover, challenge with taurocholate increased activation of trypsinogen in the pancreas. Notably, TLR2 gene-deficient mice exhibited a similar phenotype to wild-type mice after challenge with taurocholate. In contrast, tissue damage, pancreatic and lung myeloperoxidase (MPO) activity, serum and pancreatic levels of CXCL2 as well as blood amylase were significantly reduced in TLR4-deficient mice exposed to taurocholate. However, taurocholate-induced activation of trypsinogen was intact in TLR4-deficient mice.
Our data suggest a role for TLR4 but not TLR2 in the pathogenesis of severe AP in mice.
中性粒细胞浸润是急性胰腺炎（AP）病理生理学的关键调节因子，尽管 Toll 样受体（TLRs）在 AP 中的作用仍不清楚。本研究旨在确定 TLR2 和 TLR4 在重症 AP 中白细胞募集和组织损伤中的作用。
通过逆行胰管内注入牛磺胆酸钠在野生型、TLR2 和 TLR4 缺陷型小鼠中诱导 AP。在诱导 AP 后 24 小时收集样本。
牛磺胆酸钠刺激导致明显的胰腺损伤，特征为腺泡细胞坏死、中性粒细胞浸润、局灶性出血和水肿形成，以及胰腺和血清中淀粉酶和 CXCL2（巨噬细胞炎症蛋白-2）水平升高。此外，牛磺胆酸钠刺激增加了胰腺中胰蛋白酶原的激活。值得注意的是，TLR2 基因缺陷型小鼠在接受牛磺胆酸钠刺激后表现出与野生型小鼠相似的表型。相比之下，TLR4 缺陷型小鼠暴露于牛磺胆酸钠后，组织损伤、胰腺和肺髓过氧化物酶（MPO）活性、血清和胰腺 CXCL2 水平以及血淀粉酶明显降低。然而，TLR4 缺陷型小鼠中牛磺胆酸钠诱导的胰蛋白酶原激活是完整的。
我们的数据表明 TLR4 而不是 TLR2 在小鼠重症 AP 的发病机制中起作用。
