Impaired Uptake of Serotonin by Platelets From Patients With Irritable Bowel Syndrome Correlates With Duodenal Immune Activation
Impaired Uptake of Serotonin by Platelets From Patients With Irritable Bowel Syndrome Correlates With Duodenal Immune Activation
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DOI：
10.1053/j.gastro.2011.01.052
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发表时间：
2011-05-01
期刊：
影响因子：
29.4
通讯作者：
Spiller, Robin C.
中科院分区：
文献类型：
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作者：
Foley, Stephen;Garsed, Klara;Spiller, Robin C.
背景与目的：肠易激综合征伴腹泻（IBS-D）患者的粘膜5-羟色胺（5-HT）可用性增加，可能是因为免疫激活降低了5-HT转运蛋白（SERT）的活性。我们研究了IBS-D患者十二指肠粘膜和血小板SERT与免疫激活的关系。方法：我们定量了29名健康志愿者（HV）、20名IBS-D患者和20名未经治疗的乳糜泻患者血液样本中的粘膜上皮内淋巴细胞（IEL）、肥大细胞和肠嗜铬细胞，测量了粘膜样本中SERT信使RNA（mRNA）的水平，并评估了血小板对5-HT的摄取和3 H-帕罗西汀的血小板膜结合。结果：与HV相比，IBS-D或乳糜泻患者IEL和肥大细胞数量增加（均P <0.001）。在IBS-D或乳糜泻患者的粘膜中，SERT mRNA水平降低，并与IEL数量呈负相关（r =-0.72，P < .0001）。IBS-D或乳糜泻患者血小板对5-HT的摄取减少（平均值分别为17.1 ± 3.5和28.3 ± 4.1 nmol . min（-1）。mg（-1））与HV（50.8 +/- 8.0 nmol . min（-1）。mg（-1），P < .01和P = .05）。帕罗西汀与IBS-D患者血小板膜的结合率（中位数[四分位数间距]，226 [92-405] fmol/mg蛋白质）显著高于HV患者（109 [69-175] fmol/mg蛋白质），并与5-HT的血小板摄取呈负相关（r =-0.62，P = 0.03）。IBS-D患者孵育活检样本中类胰蛋白酶的释放显著增加（2.2 [0.42-3.5] vs 0.50 [0.25-0.86] ng）。mL（-1）。mg（-1）HV; P = .03）。结论：IBS-D患者血小板SERT降低，并与SERT mRNA水平降低和十二指肠免疫激活相关。
BACKGROUND & AIMS: Patients with irritable bowel syndrome with diarrhea (IBS-D) have increased mucosal serotonin (5-hydroxytryptamine [5-HT]) availability, possibly because immune activation reduces activity of the 5-HT transporter (SERT). We investigated the relationship between mucosal and platelet SERT and immune activation of the duodenal mucosa in patients with IBS-D. METHODS: We quantified mucosal intraepithelial lymphocytes (IELs), mast cells, and enterochromaffin cells in blood samples, measured levels of SERT messenger RNA (mRNA) in mucosal samples, and assessed platelet uptake of 5-HT and platelet membrane binding of 3H-paroxetine in samples from 29 healthy volunteers (HVs), 20 patients with IBS-D, and 20 untreated patients with celiac disease. RESULTS: Patients with IBS-D or celiac disease had increased numbers of IELs and mast cells compared with HVs (both P < .001). Levels of SERT mRNA were reduced in the mucosa of patients with IBS-D or celiac disease and were inversely correlated with numbers of IELs (r = -0.72, P < .0001). Uptake of 5-HT by platelets from patients with IBS-D or celiac disease was reduced (mean, 17.1 +/- 3.5 and 28.3 +/- 4.1 nmol . min(-1) . mg(-1), respectively) compared with HVs (50.8 +/- 8.0 nmol . min(-1) . mg(-1), P < .01 and P = .05, respectively). Binding of paroxetine to membranes of platelets from patients with IBS-D (median [interquartile range], 226 [92-405] fmol/mg protein) was significantly greater than that from HVs (109 [69-175] fmol/mg protein) and correlated inversely with platelet uptake of 5-HT (r = -0.62, P = .03). Tryptase release from incubated biopsy samples was significantly increased in patients with IBS-D (2.2 [0.42-3.5] vs 0.50 [0.25-0.86] ng . mL(-1) . mg(-1) for HVs; P = .03). CONCLUSIONS: Platelet SERT is reduced in IBS-D and associated with reduced levels of SERT mRNA and duodenal immune activation.