Miura S, Tsuzuki Y, Kurose I, Suematsu M, Shigematsu T, Kimura H, Higuchi H, Serizawa H, Yagita H, Okumura K, Granger D N, Ishii H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Am J Physiol. 1996 Aug;271(2 Pt 1):G282-92. doi: 10.1152/ajpgi.1996.271.2.G282.
Although lymphocyte-endothelial cell interactions represent a key step in controlling the recruitment of lymphocytes into gut-associated tissues, its dynamic process in microvessels of lymphoid (Peyer's patches) and nonlymphoid (villus) regions of the small bowel remains poorly understood. We monitored the migration of fluorescence-labeled T lymphocytes into normal and lipopolysaccharide (LPS)-inflamed rat intestinal microvessels using intravital microscopy. In Peyer's patches, T lymphocytes selectively adhered to postcapillary venules, although such selectivity was not observed in submucosal venules of villi. T lymphocytes exhibited rolling behavior followed by firm adhesion in microvessels of both the Peyer's patches and the villi, with both types of adhesive interaction being mediated by alpha 4-integrins. The enhanced rolling and adherence of lymphocytes observed in Peyer's patches and submucosal venules of villi of LPS-treated rats were preceded by a reduction in shear rate and were mediated largely by alpha 4-integrins and partly by beta 2-integrins. In capillaries of intestinal mucosa, lymphocyte adherence occurred without rolling and was independent of alpha 4-integrins. LPS also significantly increased adherence of lymphocytes to villus capillaries, which was not mediated by either alpha 4- or beta 2-integrin. These observations demonstrate significant heterogeneity of lymphocyte-endothelial cell interactions within different regions of the intestinal mucosa.
尽管淋巴细胞与内皮细胞的相互作用是控制淋巴细胞募集至肠道相关组织的关键步骤,但其在小肠淋巴样(派尔集合淋巴结)和非淋巴样(绒毛)区域微血管中的动态过程仍知之甚少。我们使用活体显微镜监测荧光标记的T淋巴细胞向正常和脂多糖(LPS)炎症大鼠肠道微血管的迁移。在派尔集合淋巴结中,T淋巴细胞选择性地黏附于毛细血管后微静脉,而在绒毛的黏膜下微静脉中未观察到这种选择性。T淋巴细胞在派尔集合淋巴结和绒毛的微血管中均表现出滚动行为,随后牢固黏附,两种黏附相互作用均由α4整合素介导。在LPS处理大鼠的派尔集合淋巴结和绒毛黏膜下微静脉中观察到的淋巴细胞滚动和黏附增强之前,剪切速率降低,且主要由α4整合素介导,部分由β2整合素介导。在肠黏膜毛细血管中,淋巴细胞黏附时无滚动现象,且不依赖于α4整合素。LPS还显著增加了淋巴细胞对绒毛毛细血管的黏附,这并非由α4或β2整合素介导。这些观察结果表明肠黏膜不同区域内淋巴细胞与内皮细胞相互作用存在显著异质性。