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乳糜泻和克罗恩病患者小肠中的中性粒细胞和嗜酸性粒细胞受累情况:粒细胞颗粒成分分泌率及免疫组化定位研究

Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn's disease: studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents.

作者信息

Hällgren R, Colombel J F, Dahl R, Fredens K, Kruse A, Jacobsen N O, Venge P, Rambaud J C

机构信息

Department of Internal Medicine, University Hospital, Uppsala, Sweden.

出版信息

Am J Med. 1989 Jan;86(1):56-64. doi: 10.1016/0002-9343(89)90230-1.

Abstract

PURPOSE

The concentrations of myeloperoxidase (MPO), a neutrophil granule constituent, and eosinophil cationic protein (ECP), a specific eosinophil granule protein, were measured in jejunal perfusion fluid in an attempt to elucidate the neutrophil and eosinophil involvement of the small bowel in health and disease.

PATIENTS AND METHODS

The control group consisted of 14 males and two females. Ten patients (seven males and three females) with Crohn's disease and seven patients (two males and five females) with celiac disease were also studied; in addition, one patient with relapsing giardiasis, one patient with giardiasis and complete absence of plasma cells in small intestinal lamina propria, and one patient with selective IgA deficiency and no IgA plasma cells in duodeno-jejunal lamina propria were evaluated. Segmental perfusion of the jejunum was performed according to a previously described method. MPO and ECP were measured by radioimmunoassays.

RESULTS

In healthy control subjects, the concentrations of both granule proteins were in a narrow range and much higher than would have been anticipated from passive leakage from circulating blood. In patients with celiac disease, the perfusion fluid concentrations of MPO and ECP were on average 3.5 and eight times, respectively, higher than the values seen in the controls. The jejunal segment perfused in patients with Crohn's disease was endoscopically and histologically normal. The perfusion fluid concentrations of MPO and ECP were increased 3.5 and two times, respectively, compared with that in the control subjects. Both patient groups and the control group had similar perfusion fluid concentrations of albumin. Data on MPO and ECP expressed as jejunal secretion rates gave the same differences between patients and controls as just described for the jejunal fluid concentrations. Immunohistochemical studies of jejunal biopsy specimens from another group of patients with celiac disease demonstrated a prominent extracellular deposit of ECP in the lamina propria of the atrophic intestinal mucosa, whereas the release of neutrophil constituents (cathepsin G, MPO) was scarce. In Crohn's disease, an extracellular degranulation of ECP and, to a lesser extent, of cathepsin G was observed in relation to ulcerations only.

CONCLUSION

Data obtained indicate that the local release of neutrophil and eosinophil granule components is enhanced in the jejunal tissue from patients with celiac sprue and Crohn's disease. The prominent extracellular deposit of eosinophil granule constituents with cytotoxic properties at the site of inflammatory intestinal lesions in celiac sprue might reflect a pathophysiologic mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

目的

测定空肠灌洗液中髓过氧化物酶(MPO,一种中性粒细胞颗粒成分)和嗜酸性粒细胞阳离子蛋白(ECP,一种特异性嗜酸性粒细胞颗粒蛋白)的浓度,以试图阐明小肠在健康和疾病状态下中性粒细胞和嗜酸性粒细胞的参与情况。

患者与方法

对照组由14名男性和2名女性组成。还研究了10例克罗恩病患者(7名男性和3名女性)和7例乳糜泻患者(2名男性和5名女性);此外,评估了1例复发性贾第虫病患者、1例贾第虫病且小肠固有层完全缺乏浆细胞的患者,以及1例选择性IgA缺乏且十二指肠 - 空肠固有层无IgA浆细胞的患者。根据先前描述的方法进行空肠节段灌注。通过放射免疫测定法测量MPO和ECP。

结果

在健康对照受试者中,两种颗粒蛋白的浓度处于狭窄范围内,且远高于从循环血液被动渗漏所预期的水平。在乳糜泻患者中,MPO和ECP的灌洗液浓度平均分别比对照组中所见的值高3.5倍和8倍。克罗恩病患者中被灌注的空肠节段在内镜和组织学上是正常的。与对照受试者相比,MPO和ECP的灌洗液浓度分别增加了3.5倍和2倍。两个患者组和对照组的白蛋白灌洗液浓度相似。以空肠分泌率表示的MPO和ECP数据在患者和对照组之间显示出与上述空肠液浓度相同的差异。对另一组乳糜泻患者的空肠活检标本进行免疫组织化学研究表明,萎缩性肠黏膜固有层中ECP有显著的细胞外沉积,而中性粒细胞成分(组织蛋白酶G、MPO)的释放很少。在克罗恩病中,仅在溃疡处观察到ECP以及程度较轻的组织蛋白酶G的细胞外脱颗粒。

结论

所获得的数据表明,乳糜泻和克罗恩病患者空肠组织中中性粒细胞和嗜酸性粒细胞颗粒成分的局部释放增强。在乳糜泻的炎症性肠病变部位,具有细胞毒性特性的嗜酸性粒细胞颗粒成分的显著细胞外沉积可能反映了一种病理生理机制。(摘要截短至400字)

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