Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis.
Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis.
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DOI：
10.1371/journal.pone.0060529
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ceyhan GO
中科院分区：
文献类型：
--
作者：
Demir IE;Schorn S;Schremmer-Danninger E;Wang K;Kehl T;Giese NA;Algül H;Friess H;Ceyhan GO
胰腺神经炎是胰腺神经病的组织病理学特征，与胰腺癌(PCA)和慢性胰腺炎(CP)的腹部神经病理性痛感有关。然而，构成胰腺神经炎的炎性细胞亚型及其与PCa和CP的神经病理性疼痛综合征的相关性尚不清楚。对前列腺癌(n = 2 0)和慢性胰腺炎(n = 2 0)患者胰腺神经炎病变内的炎性细胞进行免疫标记和比色定量，并用CD6 8(巨噬细胞)、CD8(细胞毒性T淋巴细胞)、CD4(辅助性T细胞)、CD2 0(B淋巴细胞)、NCL-PC(浆细胞)、中性粒细胞弹性蛋白酶、PrG2(嗜酸性粒细胞)、抗肥大细胞(MC)类胰蛋白酶与痛觉相关。MC糜酶免疫双标记法分析神经周围肥大细胞亚型。分析蛋白水解酶激活受体1(PAR-1)和PAR-2(PAR-2)在PCa和CP中的表达和神经免疫反应性，并与患者的疼痛状态相关联。在PCa和CP中，细胞毒性T淋巴细胞(Pca：35%，Cp：33%)、巨噬细胞(Pca：39%，Cp：33%)和MC(Pca：21%，Cp：27%)主要浸润神经。在这两个实体中，神经病理性痛感与神经周MC的特异性增加有关(无痛的PCa：14%对有疼痛的PCa：31%；无痛的CP：19%对有疼痛的CP：34%)，而不影响其他炎症细胞亚型的频率。绝大多数MC含有MC糜酶。PAR-1和PAR-2的表达与PCa和CP患者的痛感无相关性。PC和CP的胰神经炎由细胞毒性T淋巴细胞、巨噬细胞和MC组成。在PCa和CP所致的神经病理性疼痛中，胰腺内神经周围MC的特异性丰富表明MC诱导的胰腺内脏高敏感性的存在。因此，在内脏疼痛的产生过程中，胰腺和肠道神经病变似乎分享了类似类型的神经免疫相互作用。
Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown. Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients. In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients. Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.
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影响因子：
29.4
作者：
Hoogerwerf, WA;Shenoy, M;Pasricha, PJ
通讯作者：
Pasricha, PJ
影响因子：
2.4
作者：
Hoogerwerf WA;Gondesen K;Xiao SY;Winston JH;Willis WD;Pasricha PJ
通讯作者：
Pasricha PJ
影响因子：
29.4
作者：
Ceyhan, Gueralp O.;Bergmann, Frank;Friess, Helmut
通讯作者：
Friess, Helmut
DOI：
10.1016/j.bpg.2007.10.016
发表时间：
2008-01-01
影响因子：
3.2
作者：
Ceyhan, Guralp O.;Michalski, Christoph W.;Friess, Helmut
通讯作者：
Friess, Helmut
影响因子：
29.4
作者：
DiSebastiano, P;Fink, T;Buchler, MW
通讯作者：
Buchler, MW