Zhang Y, Ramos B F, Jakschik B A
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Invest. 1991 Sep;88(3):841-6. doi: 10.1172/JCI115385.
Immune complex-induced injury is an important pathogenic factor in antibody-mediated nephritis, systemic lupus erythematosus, rheumatoid arthritis, and other diseases. In this study we investigated the role mast cells in immune complex-mediated injury in mouse skin. Reverse Arthus reaction was induced in mast cell-deficient WBB6F1-W/Wv mice and their congenic controls (WBB6F1(-)+/+). Serial skin sections were evaluated for neutrophil infiltration, edema, and hemorrhage. In WBB6F1-W/Wv mice the neutrophil influx was only 40% and edema 60% of that in congenic controls. Hemorrhage was also significantly reduced in the mast cell-deficient mice. After mast cell reconstitution, the magnitude of the reaction in WBB6F1-W/Wv was equivalent to that in WBB6F1(-)+/+ mice. Mast cell release in reverse Arthus reaction was evaluated by measuring fluorescence intensity after avidin-FITC staining of mast cell granules. There was a 70% decrease in fluorescence intensity. The 5-lipoxygenase inhibitor A-63162 significantly decreased neutrophil accumulation (40%), edema (60%), and hemorrhage in WBB6F1(-)+/+, but not in mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/Wv mice restored the effect of A-63162. The results indicate that mast cells and their mediators, including leukotrienes, make an important contribution to reverse Arthus reaction.
免疫复合物诱导的损伤是抗体介导性肾炎、系统性红斑狼疮、类风湿性关节炎及其他疾病的重要致病因素。在本研究中，我们调查了肥大细胞在小鼠皮肤免疫复合物介导损伤中的作用。在肥大细胞缺陷的WBB6F1-W/Wv小鼠及其同基因对照（WBB6F1(-)+/+）中诱导反向阿瑟斯反应。对连续的皮肤切片进行中性粒细胞浸润、水肿和出血情况评估。在WBB6F1-W/Wv小鼠中，中性粒细胞流入量仅为同基因对照的40%，水肿为60%。肥大细胞缺陷小鼠的出血情况也显著减少。肥大细胞重建后，WBB6F1-W/Wv小鼠的反应程度与WBB6F1(-)+/+小鼠相当。通过对肥大细胞颗粒进行抗生物素蛋白-异硫氰酸荧光素（avidin-FITC）染色后测量荧光强度来评估反向阿瑟斯反应中肥大细胞的释放情况。荧光强度降低了70%。5-脂氧合酶抑制剂A-63162显著降低了WBB6F1(-)+/+小鼠的中性粒细胞聚集（40%）、水肿（60%）和出血，但对肥大细胞缺陷小鼠无效。WBB6F1-W/Wv小鼠的肥大细胞重建恢复了A-63162的作用。结果表明，肥大细胞及其介质（包括白三烯）对反向阿瑟斯反应有重要贡献。
