Fujimori Keita, Oh-i Keiko, Takeuchi Masaru, Yamakawa Naoyuki, Hattori Takaaki, Kezuka Takeshi, Keino Hiroshi, Suzuki Jun, Goto Hiroshi, Sakai Jun-ichi, Usui Masahiko
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Graefes Arch Clin Exp Ophthalmol. 2008 Feb;246(2):285-90. doi: 10.1007/s00417-007-0659-5. Epub 2007 Aug 10.
Behçet disease (BD) is manifested by recurrent acute iridocyclitis with hypopyon in the active phase, which regresses spontaneously. Hypopyon consists of inflammatory cells infiltrating the eye, with polymorphonuclear cells (PMNs) as the main component. The present study was conducted to investigate the apoptosis property of PMNs in BD patients with uveitis.
PMNs were purified from peripheral blood cells of BD patients with uveitis in the active or remission phase and were cultured for 12 hours. In some cultures, lipopolysaccharide (LPS), antagonistic anti-TNFalpha antibody, agonistic anti-Fas antibody, or Fas:Fc fusion protein was added. At the end of cultures, apoptotic cells were evaluated by Annexin V expression using flow cytometry.
Spontaneous apoptosis of PMNs showed lower levels in the remission phase of BD-related uveitis compared with the active phase or healthy controls. The lower level of PMN apoptosis in the remission phase of uveitis in BD remained even by stimulation with LPS, anti-TNFalpha antibody, or Fas:Fc fusion protein, which was abolished in the presence of agonistic anti-Fas antibody.
In BD patients, the apoptosis of PMNs was reduced in the remission phase of uveitis and restored in the active phase, which arose from the apoptotic cell death in part via Fas-Fas ligand interaction.
白塞病(BD)在活动期表现为复发性急性虹膜睫状体炎伴前房积脓,可自行消退。前房积脓由浸润眼部的炎症细胞组成,以多形核细胞(PMN)为主要成分。本研究旨在探讨BD葡萄膜炎患者中PMN的凋亡特性。
从活动期或缓解期BD葡萄膜炎患者的外周血细胞中纯化PMN,并培养12小时。在一些培养物中,加入脂多糖(LPS)、抗TNFα抗体拮抗剂、抗Fas抗体激动剂或Fas:Fc融合蛋白。培养结束时,使用流式细胞术通过膜联蛋白V表达评估凋亡细胞。
与活动期或健康对照相比,BD相关性葡萄膜炎缓解期PMN的自发凋亡水平较低。即使在用LPS、抗TNFα抗体或Fas:Fc融合蛋白刺激后,BD葡萄膜炎缓解期PMN凋亡水平仍较低,而在抗Fas抗体激动剂存在的情况下这种情况被消除。
在BD患者中,葡萄膜炎缓解期PMN的凋亡减少,活动期恢复,这部分是通过Fas-Fas配体相互作用导致的凋亡细胞死亡引起的。