Zhang Y, Ramos B F, Jakschik B A
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110.
Immunology. 1992 Nov;77(3):422-7.
Immune injury of the basement membrane occurs in various human diseases. In the present study, an antibody specific for the basement membrane of mouse skin was injected i.d. into mast cell-deficient WBB6F1-W/Wv mice and their congenic controls, WBB6F1-(+/+). Vascular permeability changes, oedema and fibrin deposition were assessed. Plasma permeation, evaluated by dye exudation, was time and dose dependent in both groups of animals, but significantly less in WBB6F1-W/Wv than in normal mice. At 30 min, the time of maximum in congenic controls, extravasation of the dye was 60% less in mast cell-deficient than in WBB6F1-(+/+) mice. Pyrilamine decreased exudation by 40% in normal but not in WBB6F1-W/Wv mice, indicating that the mast cell mediator histamine contributes to the increase in vascular permeability. Mast cell deficiency also markedly reduced fibrin deposition as assessed by direct immunostaining. Oedema, measured as skin thickness, was 60% less in WBB6F1-W/Wv mice than in their congenic controls. A 5-lipoxygenase blocker inhibited plasma exudation and oedema in normal but not in WBB6F1-W/Wv mice. This indicates that leukotrienes are involved in these processes and that mast cells are important for their production. Local mast cell reconstitution restored dye extravasation and oedema to normal levels as well as the effect of the 5-lipoxygenase inhibitor. These findings show that mast cells and their mediators participate in these inflammatory processes which were initiated by the deposition of IgG on the skin basement membrane.
基底膜的免疫损伤发生于多种人类疾病中。在本研究中，将一种针对小鼠皮肤基底膜的特异性抗体皮内注射到肥大细胞缺陷型WBB6F1-W/Wv小鼠及其同基因对照WBB6F1-(+/+)小鼠体内。评估血管通透性变化、水肿和纤维蛋白沉积情况。通过染料渗出评估的血浆渗透在两组动物中均呈时间和剂量依赖性，但WBB6F1-W/Wv小鼠中的血浆渗透明显低于正常小鼠。在同基因对照的最大渗透时间30分钟时，肥大细胞缺陷型小鼠的染料外渗比WBB6F1-(+/+)小鼠少60%。吡苄明使正常小鼠的渗出减少40%，但对WBB6F1-W/Wv小鼠无效，这表明肥大细胞介质组胺促成了血管通透性的增加。通过直接免疫染色评估发现，肥大细胞缺陷也显著减少了纤维蛋白沉积。以皮肤厚度衡量的水肿，WBB6F1-W/Wv小鼠比其同基因对照少60%。一种5-脂氧合酶阻滞剂抑制正常小鼠的血浆渗出和水肿，但对WBB6F1-W/Wv小鼠无效。这表明白三烯参与了这些过程，且肥大细胞对其产生很重要。局部肥大细胞重建使染料外渗和水肿恢复到正常水平，同时也恢复了5-脂氧合酶抑制剂的作用。这些发现表明，肥大细胞及其介质参与了由IgG沉积在皮肤基底膜上引发的这些炎症过程。
