Kraneveld A D, Muis T, Koster A S, Nijkamp F P
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Am J Physiol. 1998 May;274(5):G832-9. doi: 10.1152/ajpgi.1998.274.5.G832.
Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropetides. Within 1 h after challenge, a significant increase in vascular permeability was found in vivo as well as in vitro. This was associated with a DTH-specific increase in RMCP II in the serum, indicating mucosal mast cell activation. In addition, doxantrazole treatment and caspaicin pretreatment resulted in a significant inhibition of the DTH-induced vascular leakage and an increase in serum RMCP II. These findings are consistent with an important role for mucosal mast cells in early vascular leakage changes of intestinal DTH reactions. In addition, sensory nervous control of mucosal mast cell activation early after challenge is demonstrated.
此前研究表明,在激发前后使黏膜肥大细胞耗竭和稳定,对减轻大鼠小肠的迟发型超敏反应(DTH)非常有效。本研究进一步探讨了黏膜肥大细胞在肠道DTH反应早期阶段的作用。在给5天前用二硝基苯致敏的大鼠进行胃内激发后1小时内,测定其体内小肠血管通透性及大鼠肥大细胞蛋白酶II(RMCP II)的血清水平。另外使用一组大鼠研究体外激发后分离的血管灌注小肠的血管通透性。为研究肥大细胞稳定对DTH反应早期事件的影响,使用了多沙唑嗪。通过新生大鼠辣椒素诱导感觉神经肽耗竭的方法研究感觉神经的影响。激发后1小时内,在体内和体外均发现血管通透性显著增加。这与血清中RMCP II的DTH特异性增加相关,表明黏膜肥大细胞被激活。此外,多沙唑嗪治疗和辣椒素预处理可显著抑制DTH诱导的血管渗漏,并使血清RMCP II增加。这些发现与黏膜肥大细胞在肠道DTH反应早期血管渗漏变化中起重要作用一致。此外,还证明了激发后早期感觉神经对黏膜肥大细胞激活的控制作用。