Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome
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DOI:
10.1053/j.gastro.2003.11.055
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发表时间:
2004-03-01
期刊:
影响因子:
29.4
通讯作者:
Corinalidesi, R
Corinalidesi, R
中科院分区:
医学1区
文献类型:
--
作者:
Barbara, G;Stanghellini, V;Corinalidesi, R

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背景与目的:肠易激综合征(IBS)腹痛感知的机制尚不清楚。肠道肥大细胞浸润可能会扰乱神经功能,导致症状感知。我们评估了 IBS 患者的结肠肥大细胞浸润、介质释放、与粘膜神经支配的空间相互作用及其与腹痛的相关性。方法:IBS 患者根据罗马 11 标准进行诊断,并根据经过验证的问卷对腹痛进行量化。通过免疫组织化学方法鉴定结肠粘膜肥大细胞,并通过计算机辅助计数方法进行定量。通过免疫酶法分析肥大细胞类胰蛋白酶和组胺释放。用电子显微镜评估肠神经到肥大细胞的距离。结果:44 名 IBS 患者中有 34 名 (77%) 与对照组相比,肥大细胞占据的粘膜面积增加(分别为 9.2% +/- 2.5% 与 3.3 +/- 0.8%;P < 0.001)。脱颗粒肥大细胞的数量增加了 150%(分别为 4.76 +/- 3.18/视野 vs. 2.42 +/- 2.26/视野;P = 0,026)。 IBS 中粘膜类胰蛋白酶含量增加,肥大细胞自发释放更多类胰蛋白酶(分别为 3.22 +/- 3.48 pmol/min/mg 与 0.87 +/- 0.65 pmol/min/mg;P = 0.015)和组胺(分别为 339.7 +/- 59.0 ng/g 与 169.3 +/- 130.6 ng/g); P 0.015)。与对照组相比,IBS 中位于神经纤维 5 μm 内的肥大细胞为 7.14 +/- 3.87 个/视野,而 IBS 为 2.27 +/- 1.63 个/视野(P < 0.001)。只有靠近神经的肥大细胞与腹痛/不适的严重程度和频率显着相关(分别为 P < 0.001 和 P = 0.003)。结论:结肠肥大细胞浸润和靠近粘膜神经支配的介质释放可能有助于 IBS 患者的腹痛感觉。
Background&Aims: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. Methods: IBS patients were diagnosed according to Rome 11 criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. Results: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/ field vs. 2.42 +/- 2.26/field, respectively; P = 0,026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/ mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P 0.015). Mast cells located within 5 mu m of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). Conclusions: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.