Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice.
Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice.
复制标题
乳糖诱导中性粒细胞和巨噬细胞的表型和功能变化，以减轻小鼠急性胰腺炎。
DOI：
10.3389/fimmu.2018.00751
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Pan LL;Deng YY;Wang R;Wu C;Li J;Niu W;Yang Q;Bhatia M;Gudmundsson GH;Agerberth B;Diana J;Sun J
急性胰腺炎（acute pancreatitis，AP）是临床常见的急腹症之一，目前尚无特效的药物或营养治疗方法。乳糖是一种大量营养素，是宿主天然免疫应答的诱导剂，具有免疫调节功能。本研究旨在探讨乳糖对实验性AP小鼠胰腺免疫功能的潜在调节作用及其与营养素之间的相互作用。我们发现，无论是预防性或治疗性治疗的乳糖时间依赖性降低AP的严重程度，胰腺水肿，血清淀粉酶水平，胰腺髓过氧化物酶活性降低，以及胰腺损伤的组织学检查证明。总体而言，乳糖促进了胰腺中的调节性细胞因子环境，并减少了炎性中性粒细胞和巨噬细胞的浸润。在腺泡细胞上，乳糖能够抑制雨蛙素诱导的炎症信号通路，并抑制趋化因子肿瘤坏死因子（TNF）-α和单核细胞趋化蛋白-1的产生。此外，乳糖作用于胰腺浸润的巨噬细胞，增加白细胞介素-10和减少肿瘤坏死因子α的产生。值得注意的是，乳糖治疗逆转了AP相关的活化中性粒细胞浸润。最后，乳糖对中性粒细胞浸润的影响被半乳糖凝集素-3拮抗剂模仿，表明乳糖的潜在内源性靶点。总之，目前的研究证明了乳糖对缓解AP的免疫调节作用，并表明其作为控制AP的方便，增值的治疗性宏量营养素的潜力，并降低其全身并发症的风险。
Acute pancreatitis (AP) is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications.
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影响因子：
3.7
作者：
Cederlund A;Kai-Larsen Y;Printz G;Yoshio H;Alvelius G;Lagercrantz H;Strömberg R;Jörnvall H;Gudmundsson GH;Agerberth B
通讯作者：
Agerberth B
影响因子：
6.3
作者：
Ishibashi, Toshiaki;Zhao, Haifeng;Ito, Tetsuhide
通讯作者：
Ito, Tetsuhide
影响因子：
6.3
作者：
Kanak, Mazhar A.;Shahbazov, Rauf;Naziruddin, Bashoo
通讯作者：
Naziruddin, Bashoo
DOI：
10.1073/pnas.0903497106
发表时间：
2009-08-25
影响因子：
11.1
作者：
Chen, Huan-Yuan;Fermin, Agnes;Liu, Fu-Tong
通讯作者：
Liu, Fu-Tong
树突状细胞促进急性胰腺炎小鼠的胰腺生存力。
影响因子：
29.4
作者：
Bedrosian AS;Nguyen AH;Hackman M;Connolly MK;Malhotra A;Ibrahim J;Cieza-Rubio NE;Henning JR;Barilla R;Rehman A;Pachter HL;Medina-Zea MV;Cohen SM;Frey AB;Acehan D;Miller G
通讯作者：
Miller G