Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1
Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1
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DOI：
10.1002/art.11268
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发表时间：
2003-11-01
影响因子：
--
通讯作者：
Nagasawa, K
中科院分区：
文献类型：
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作者：
Tada, Y;Koarada, S;Nagasawa, K
Objective.血小板内皮细胞粘附分子1（PECAM-1; CD 31）是免疫球蛋白超家族的成员，在血小板、白细胞和内皮细胞中表达。已显示PECAM-1在白细胞的跨内皮迁移中起作用，并且在其胞质尾区中含有基于免疫受体酪氨酸的抑制基序，并抑制细胞应答。我们研究了PECAM-1在胶原诱导性关节炎（CIA）发展中的作用。在PECAM-1缺陷型DBA/1小鼠中诱导CIA。观察关节炎发生率及关节炎指数。测定抗II型胶原（抗CII）抗体水平和淋巴结细胞和脾细胞产生的干扰素-γ（IFN-γ）。用染料标记来自关节炎PECAM-1缺陷型和野生型小鼠的淋巴细胞，转移到关节炎PECAM-1（+/-）小鼠，并检查细胞向发炎关节的迁移。PECAM-1缺陷小鼠显示关节炎的加速发作和仅在早期阶段增加的严重性。抗-CII抗体水平也在早期阶段增加。来自PECAM-1缺陷小鼠的淋巴结细胞和脾细胞对CII的应答产生的IFN γ高于野生型小鼠。来自关节炎PECAM-1缺陷小鼠的淋巴细胞显示加速迁移至发炎关节，但不迁移至淋巴结或脾脏。抗CII抗体诱导的关节炎在PECAM-1缺陷型和野生型小鼠中的发展相似。这些结果表明，PECAM-1负调节体液和细胞介导的免疫反应和淋巴细胞迁移到关节，因此，CIA的发展。此外，PECAM-1在白细胞跨内皮迁移中的作用在该模型中似乎是多余的。
Objective. Platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) is a member of the immunoglobulin superfamily that is expressed in platelets, leukocytes, and endothelial cells. PECAM-1 has been shown to play a role in transendothelial migration of leukocytes and contains immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail and inhibits cellular responses. We examined the role of PECAM-1 in the development of collagen-induced arthritis (CIA).Methods. CIA was induced in PECAM-1-deficient DBA/1 mice. The incidence of arthritis and the arthritis index were examined. Anti-type II collagen (anti-CII) antibody levels and interferon-gamma (IFNgamma) production by lymph node cells and spleen cells were determined. Lymphocytes from arthritic PECAM-1-deficient and wild-type mice were labeled with dye, transferred to arthritic PECAM-1(+/-) mice, and cell migration to inflamed joints was examined.Results. PECAM-1-deficient mice showed accelerated onset of arthritis and increased severity only during the early phase. Anti-CII antibody levels were also increased during the early phase. IFNgamma production by lymph node cells and spleen cells from PECAM-1-deficient mice in response to CII was higher than that in wild-type mice. Lymphocytes from arthritic PECAM-1-deficient mice showed accelerated migration to inflamed joints, but not lymph nodes or spleen. The development of anti-CII antibody-induced arthritis was similar in PECAM-1-deficient and wild-type mice.Conclusion. These results indicate that PECAM-1 negatively regulates humoral and cell-mediated immune responses and lymphocyte migration into joints and, consequently, the development of CIA. In addition, the role of PECAM-1 in the transendothelial migration of leukocytes appears to be redundant in this model.