Tomida S, Hasegawa T, Takeuchi M, Niimi N, Ueda M, Kaneda T, Tanaka T, Tamatani T, Miyasaka M, Yoshikai Y
Department of Oral Surgery, Nagoya University School of Medicine, Japan.
Int Immunol. 1994 Jul;6(7):955-61. doi: 10.1093/intimm/6.7.955.
To investigate the significance of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) in host defense against infection with intracellular parasites, we examined the effects of in vivo pretreatment with mAbs to ICAM-1 (1A29) and LFA-1 alpha (WT-1) on the protection against infection with Listeria monocytogenes in Fisher F344/N rats. Expression of ICAM-1 and LFA-1 alpha molecules on T cells in spleen, liver and peritoneal cavity of rats was down-regulated after i.p. administration with daily doses of 300 micrograms of either 1A29 or WT-1 for 10 days. The survival rate of rats inoculated with viable Listeria was significantly reduced by in vivo pretreatment with 1A29 together with WT-1 for 10 days but not by in vivo pretreatment with control mAb. The numbers of bacteria in the spleen in rats pretreated with both 1A29 and WT-1 were significantly increased on day 3 and day 6 after infection with 1 x 10(7) of viable Listeria corresponding to 1/30 of LD50 to normal rats. Thus, the resistance against listerial infection was severely impaired by combinational pretreatment with mAbs in ICAM-1 and LFA-1 alpha. As shown in our previous report, the early appearance of CD3+TCR alpha beta- T cells, presumably TCR gamma delta T cells, was evident in the peritoneal cavity and liver of control rats at the early stage after listerial infection, while this was suppressed at this stage in rats pretreated with both 1A29 and WT1.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究细胞间黏附分子-1(ICAM-1)和白细胞功能相关抗原-1(LFA-1)在宿主抗细胞内寄生虫感染防御中的意义,我们检测了用抗ICAM-1单克隆抗体(1A29)和抗LFA-1α单克隆抗体(WT-1)进行体内预处理对Fisher F344/N大鼠抵抗单核细胞增生李斯特菌感染的保护作用。给大鼠腹腔注射每日剂量300微克的1A29或WT-1,连续10天,可使大鼠脾脏、肝脏和腹腔T细胞上ICAM-1和LFA-1α分子的表达下调。用1A29和WT-1联合体内预处理10天,可显著降低接种活李斯特菌大鼠的存活率,但用对照单克隆抗体进行体内预处理则无此效果。在用1A29和WT-1预处理的大鼠中,感染1×10⁷个活李斯特菌(相当于正常大鼠半数致死量的1/30)后第3天和第6天,脾脏中的细菌数量显著增加。因此,用抗ICAM-1和抗LFA-1α单克隆抗体联合预处理会严重损害对李斯特菌感染的抵抗力。如我们之前的报告所示,在李斯特菌感染早期,对照大鼠腹腔和肝脏中CD3⁺TCRαβ⁻T细胞(可能是TCRγδT细胞)早期出现明显,而在用1A29和WT1预处理的大鼠中,此现象在该阶段受到抑制。(摘要截短至250字)