The chemotactic peptide N-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat.

The chemotactic peptide N-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat.
复制标题

趋化肽 N-甲酰基甲硫氨酰-亮氨酰-苯丙氨酸增加大鼠回肠远端的粘膜通透性。

DOI:
10.1016/s0016-5085(88)80011-8
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发表时间:
1988
期刊:
影响因子:
29.4
通讯作者:
Granger,DN
Granger,DN
中科院分区:
医学1区
文献类型:
--
作者:
vonRitter,C;Sekizuka,E;Grisham,MB;Granger,DN

文献摘要

被引文献

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由腔源性细菌产物激活固有层内的粒细胞可能代表炎性肠病发病机制中的重要机制。本研究的目的是确定与N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(FMLP),吸引和激活粒细胞的细菌产品,在大鼠小肠和结肠的不同区域的粘膜通透性的管腔灌注的影响。在用溶于Tyrode溶液的FMLP(10- 3至10- 8 M)进行管腔灌注期间,使用51 Cr-乙二胺四乙酸盐的血液-管腔清除率测量粘液渗透性。在研究的肠段中,FMLP仅在回肠远端10 cm处显著增加了粘膜通透性。增加粘膜渗透性所需的最低FMLP浓度为10- 6 M。FMLP引起的粘膜通透性增加可通过用抗神经损伤血清耗竭循环中的粒细胞来预防。远端回肠对FMLP的更大敏感性与更高的组织髓过氧化物酶活性无关,但与更高的基础乙二胺四乙酸清除率相关。这些观察结果表明,对FMLP大小(5-6 μ m半径)的溶质的高基底粘膜渗透性,而不是固有层中更多数量的驻留粒细胞,使末端回肠易于发生FMLP的炎症作用。
Activation of granulocytes within the lamina propria by luminally derived bacterial products may represent an important mechanism in the pathogenesis of inflammatory bowel disease. The objective of this study was to determine the effects of luminal perfusion withN-formyl methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon. Mucosal permeability was measured using blood-to-lumen clearance of51Cr-ethylenediaminetetraacetate during luminal perfusion with FMLP (10-3to 10-8M) dissolved in Tyrode's solution. Of the bowel segments studied, mucosal permeability was significantly increased by FMLP only in the distal 10 cm of ileum. The minimal FMLP concentration required to increase mucosal permeability was 10-6M. The increased mucosal permeability induced by FMLP could be prevented by depletion of circulating granulocytes with antineutrophil serum. The greater sensitivity of the distal ileum to FMLP did not correlate with a higher tissue myeloperoxidase activity, but it was associated with a higher basal ethylene diaminetetraacetate clearance. These observations indicate that a high basal mucosal permeability to solutes the size of FMLP (5–6 Å radius), rather than a greater number of resident granulocytes in the lamina propria, predisposes the terminal ileum to the inflammatory actions of FMLP.