Ichikawa S, Goto Y, Uchino S, Kaltreider H B, Goetzl E J, Sreedharan S P
Department of Anatomy, Tokyo Medical College, Japan.
Arch Histol Cytol. 1996 Dec;59(5):443-52. doi: 10.1679/aohc.59.443.
In response to antigen inhalation, immune cells including alveolar macrophages expressing a VIP1 receptor subtype (VIP1R), lymphocytes and leukocytes participate in the inflammatory event, migrating into and from vascular regions in lung tissue of sensitized mice. To analyze these migratory mechanisms of immune cells, we immunohistochemically examined the expression of the following: cellular adhesion molecules, lymphocyte function-associated antigen-1 (LFA-1) very late activation antigen-4 (VLA-4), and the alpha V (alpha v) subunit and their respective ligands, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and fibronectine; the examination was carried out in pulmonary tissue from days 0, 2, 6 and 12 following intratracheal administration of sheep red blood cells (SRBC) as an antigen to previously sensitized mice. Two days following the antigen challenge, VIP1R-positive macrophages strongly expressing the alpha v integrin subunit were found clustered on the endothelial surface and among the aggregates of perivascularly infiltrated leukocytes. On the endothelium of arteries, veins and capillaries, alpha v immunoreactivity was prominently reduced, whereas staining for fibronectin was enhanced more than the prechallenge control level. The blood vessel endothelium was also stained positive for VCAM-1 and ICAM-1, while many of the infiltrating lymphocytes were positive for VLA-4 and LFA-1 immunolabelings. By post-challenge, day 6, delta v integrin subunit immunoreactivity was re-expressed on the blood vessel endothelium and only weakly expressed on VIP1R-positive macrophages, which were in retreat from the leukocyte-aggregating perivascular region and located in the alveoli. VLA-4 bearing lymphocytes conspicuously increased in number among the perivascular leukocytes, while immunoreactivity for LFA-1, VCAM-1, ICAM-1 and fibronectin was unchanged from that for post-challenge day 2. The results indicate that the expression of the alpha v-bearing integrin and its ligand fibronectin drastically changes as pulmonary inflammatory responses. These changes in expression of adhesion molecules during immune response may play an important role in the dynamic regulation of VIP1R-positive macrophage migration in the lung parenchymal compartment.
吸入抗原后，包括表达VIP1受体亚型（VIP1R）的肺泡巨噬细胞、淋巴细胞和白细胞在内的免疫细胞参与炎症反应，在致敏小鼠肺组织的血管区域内进出迁移。为了分析免疫细胞的这些迁移机制，我们采用免疫组织化学方法检测了以下指标的表达：细胞黏附分子、淋巴细胞功能相关抗原-1（LFA-1）、极迟活化抗原-4（VLA-4）、αV（αv）亚基及其各自的配体细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和纤连蛋白；检测在给先前致敏的小鼠气管内注射作为抗原的绵羊红细胞（SRBC）后的第0、2、6和12天，在肺组织中进行。抗原攻击后两天，发现强烈表达αv整合素亚基的VIP1R阳性巨噬细胞聚集在内皮表面以及血管周围浸润白细胞的聚集体中。在动脉、静脉和毛细血管的内皮上，αv免疫反应性显著降低，而纤连蛋白的染色比攻击前对照水平增强。血管内皮对VCAM-1和ICAM-1也呈阳性染色，而许多浸润淋巴细胞对VLA-4和LFA-1免疫标记呈阳性。攻击后第6天，血管内皮上重新表达了δv整合素亚基免疫反应性，而在VIP1R阳性巨噬细胞上仅微弱表达，这些巨噬细胞正从白细胞聚集的血管周围区域退缩并位于肺泡中。在血管周围白细胞中，携带VLA-4的淋巴细胞数量显著增加，而LFA-1、VCAM-1、ICAM-1和纤连蛋白的免疫反应性与攻击后第2天相比没有变化。结果表明，携带αv的整合素及其配体纤连蛋白的表达随着肺部炎症反应而发生剧烈变化。免疫反应过程中黏附分子表达的这些变化可能在肺实质区VIP1R阳性巨噬细胞迁移的动态调节中起重要作用。
