Role of VLA-4 in the development of allergic conjunctivitis in mice.
Role of VLA-4 in the development of allergic conjunctivitis in mice.
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发表时间：
2006-04
期刊：
影响因子：
2.2
通讯作者：
A. Fukushima;Tomoko Yamaguchi;W. Ishida;K. Fukata;H. Ueno
中科院分区：
文献类型：
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作者：
A. Fukushima;Tomoko Yamaguchi;W. Ishida;K. Fukata;H. Ueno
目的过敏性结膜炎(AC)的严重程度与嗜酸性粒细胞进入结膜的程度有关，目前认为嗜酸性粒细胞是由趋化因子和黏附分子介导的。黏附分子VLA-4及其配体血管细胞黏附分子(VCAM)-1在嗜酸性粒细胞浸润中起重要作用。然而，VLA-4在AC中的表达和功能尚未得到详细研究。我们试图确定实验性AC(EC)小鼠结膜中表达VLA-4的细胞的特征，并确定在AC中是否需要VLA-4和VCAM-1之间的相互作用才能使嗜酸性粒细胞渗入结膜。方法用豚草(RW)主动免疫Balb/c小鼠或过继转移RW致敏的脾细胞诱导EC，然后攻击RW。RW攻击后24小时，取结膜组织。用免疫组织化学和免疫荧光方法检测新生小鼠和发展成EC小鼠的结膜组织中VLA-4和VCAM-1的表达。为了探讨AC的发生是否需要VLA-4和VCAM-1的相互作用，在RW攻击前和攻击后2小时分别用抗VLA-4或抗VCAM-1抗体治疗EC。作为对照，EC发育小鼠用正常的大鼠免疫球蛋白处理。RW攻击后24小时，取结膜进行组织学分析。结果EC诱导后，表达VLA-4的细胞渗入结膜，但结膜血管周围的组成性VCAM-1表达不增强。免疫荧光分析显示，大多数浸润性结膜的T细胞表达VLA-4，但仅有一半浸润性嗜酸性粒细胞表达VLA-4。用抗VLA-4和抗VCAM-1抗体治疗可显著抑制主动免疫或脾细胞转移诱导的嗜酸性粒细胞渗入结膜。结论在EC的发生发展过程中，VLA-4和VCAM-1的相互作用是必要的，VLA-4表达的细胞在结膜组织中也有表达。
PURPOSE The severity of allergic conjunctivitis (AC) correlates with the degree of eosinophil infiltration into the conjunctiva, which is believed to be mediated by chemokines and adhesion molecules. The adhesion molecule very late antigen (VLA)-4 and its ligand, vascular cell adhesion molecule (VCAM)-1, are known to play important roles in eosinophil infiltration. However, the expression and function of VLA-4 in AC have not been investigated in detail. We sought to characterize VLA-4-expressing cells in the conjunctivas of mice that are developing experimental AC (EC) and to determine whether the interaction between VLA-4 and VCAM-1 is needed for the infiltration of eosinophils into the conjunctiva in AC. METHODS EC was induced in Balb/c mice by active immunization with ragweed (RW) or adoptive transfer of RW-primed splenocytes, followed by RW challenge. Twenty-four hours after RW challenge, the conjunctivas were harvested. The conjunctivas from naive mice or mice developing EC were evaluated for VLA-4 and VCAM-1 expression by immunohistochemistry and immunofluorescent analyses. To investigate whether the interaction between VLA-4 and VCAM-1 is needed for the genesis of AC, mice developing EC were treated with anti-VLA-4 or anti-VCAM-1 antibodies two h before and after RW challenge. As a control, EC-developing mice were treated with normal rat IgG. Twenty-four hours after RW challenge, the conjunctivas were harvested for histological analysis. RESULTS Upon induction of EC, VLA-4-expressing cells infiltrated the conjunctiva but the constitutive VCAM-1 expression around conjunctival vessels was not augmented. Immunofluorescent analyses demonstrated that most of the T cells infiltrating the conjunctiva expressed VLA-4 but only half of the infiltrating eosinophils expressed it. Treatment with both anti-VLA-4 and anti-VCAM-1 antibodies significantly suppressed the infiltration of eosinophils into the conjunctiva that was induced by either active immunization or splenocyte transfer. CONCLUSIONS These results confirm that VLA-4-expressing cells infiltrate the conjunctiva and that the interaction between VLA-4 and VCAM-1 is needed for the development of EC.