Queensland Institute of Medical Research, Brisbane, Qld., Australia.
Parasite Immunol. 2010 Nov-Dec;32(11-12):764-8. doi: 10.1111/j.1365-3024.2010.01241.x.
SerpinB2, also known as plasminogen activator inhibitor type-2, is a major product of macrophages and is upregulated during many infections. Although SerpinB2 inhibits urokinase plasminogen activator in vitro, evidence that this represents its physiological role in vivo is not compelling. We have recently shown that SerpinB2-/-mice generate enhanced Th1 responses after immunization with a Th1 immunogen. Herein,we show that Schistosoma japonicum granulomas induced liver SerpinB2 mRNA expression by >600-fold in wild-type mice. In SerpinB2-/- mice, worm and egg burden, and granuloma number and volume were unaffected. However, granulomas in these mice were associated with reduced fibrosis (as determined by Sirius red staining and image analysis) and increased iNOS, IL-6, IL-10 and TNFa and decreased Arg 1 and IL-13 mRNA expression. SerpinB2-/- mice immunized with soluble egg antigen (SEA) also showed reduced levels of SEA-specific IgG1. SerpinB2 deficiency thus promoted certain Th1 and reduced certain Th2 responses in response to this Th2 immunogen.
丝氨酸蛋白酶抑制剂 B2，也称为纤溶酶原激活物抑制剂 2 型，是巨噬细胞的主要产物，在许多感染中上调。尽管丝氨酸蛋白酶抑制剂 B2 在体外抑制尿激酶纤溶酶原激活物，但这是否代表其在体内的生理作用尚无确凿证据。我们最近表明，SerpinB2-/- 小鼠在免疫 Th1 免疫原后产生增强的 Th1 反应。在此，我们显示日本血吸虫肉芽肿使野生型小鼠肝脏 SerpinB2 mRNA 表达增加了>600 倍。在 SerpinB2-/- 小鼠中，蠕虫和卵负荷以及肉芽肿数量和体积不受影响。然而，这些小鼠的肉芽肿与减少的纤维化（通过天狼星红染色和图像分析确定）和增加的 iNOS、IL-6、IL-10 和 TNFa 以及减少的 Arg1 和 IL-13 mRNA 表达相关。用可溶性卵抗原（SEA）免疫的 SerpinB2-/- 小鼠也显示 SEA 特异性 IgG1 水平降低。因此，丝氨酸蛋白酶抑制剂 B2 缺乏促进了针对这种 Th2 免疫原的某些 Th1 和某些 Th2 反应。
