Abe Asami, Ishizu Akihiro, Ikeda Hitoshi, Hayase Hiroko, Tsuji Takahiro, Miyatake Yukiko, Tsuji Muneharu, Fugo Kazunori, Sugaya Toshiaki, Higuchi Masato, Matsuno Takeo, Yoshiki Takashi
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Int J Exp Pathol. 2004 Oct;85(4):191-200. doi: 10.1111/j.0959-9673.2004.00384.x.
Transgenic rats carrying the env-pX gene of human T-cell leukaemia virus type-I (env-pX rats) were immunized with type II collagen (CII), and chronological alterations of arthritis were compared with findings of collagen-induced arthritis (CIA) in wildtype Wistar-King-Aptekman-Hokudai (WKAH) rats. Arthritis induced by CII in env-pX rats was more severe and persisted longer than CIA in WKAH rats. To determine whether the phenomenon is caused mainly by the transgene-carrying lymphocytes or articular tissues, we immunized lethally irradiated env-pX and WKAH rats with reciprocal bone marrow cell (BMC) transplantation. A severe but transient arthritis was induced by CII in WKAH rats reconstituted by env-pX BMC (w/tB/CII rats). On the other hand, in env-pX rats reconstituted by WKAH BMC, arthritis persisted longer than in w/tB/CII rats, although the degree was less at an early phase after CII immunization. These findings suggest that articular tissues rather than the BMCs carrying the env-pX transgene play a role in the prolongation of arthritis in env-pX rats, although BMCs carrying the transgene are associated with the severity of arthritis. When inflammatory cytokines in synovial cells isolated from env-pX rats before they developed arthritis were examined, interleukin-6 (IL-6) was detected at a higher level than in synovial cells from WKAH rats, thus suggesting the critical role of IL-6 in env-pX arthritis.
用I型人类T细胞白血病病毒的env - pX基因(env - pX大鼠)构建的转基因大鼠,用II型胶原蛋白(CII)进行免疫,并将关节炎的时间变化与野生型Wistar - King - Aptekman - Hokudai(WKAH)大鼠的胶原诱导性关节炎(CIA)的结果进行比较。env - pX大鼠中由CII诱导的关节炎比WKAH大鼠中的CIA更严重且持续时间更长。为了确定该现象主要是由携带转基因的淋巴细胞还是关节组织引起的,我们用相互的骨髓细胞(BMC)移植对经致死性照射的env - pX和WKAH大鼠进行免疫。用env - pX BMC重建的WKAH大鼠(w/tB/CII大鼠)中,CII诱导了严重但短暂的关节炎。另一方面,在由WKAH BMC重建的env - pX大鼠中,关节炎持续时间比w/tB/CII大鼠更长,尽管在CII免疫后的早期阶段程度较轻。这些发现表明,在env - pX大鼠中,关节组织而非携带env - pX转基因的BMC在关节炎的延长中起作用,尽管携带转基因的BMC与关节炎的严重程度相关。当检查env - pX大鼠在发生关节炎之前分离的滑膜细胞中的炎性细胞因子时,发现白细胞介素 - 6(IL - 6)的水平高于WKAH大鼠的滑膜细胞,因此表明IL - 6在env - pX关节炎中起关键作用。