Department of Immunology, Mie University Graduate School of Medicine, Tsu, Japan.
J Thromb Haemost. 2013 Oct;11(10):1903-15. doi: 10.1111/jth.12392.
Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease-activated receptors (PARs). However, the role of thrombin in the immune response is not clear.
To evaluate whether thrombin has a modulatory role in allergic bronchial asthma.
Bronchial asthma was induced in mice by intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin or its inhibitors were administered by inhalation before each allergen challenge.
Mice with low but sustained coagulation activation had reduced allergic inflammation, and allergic asthma was inhibited by low doses of thrombin but worsened by high doses. Allergic asthma was worsened by antithrombin, argatroban, hirudin, and anti-thrombomodulin antibody. Mice with a higher level of an inhibitor of both thrombin and activated protein C had worse disease. Heterozygous PAR-1 mice had less allergic inflammation, but PAR-1 agonist worsened it. Allergic bronchial inflammation was worsened in mice that received adoptive transfer of PAR-1 agonist-treated Th2 cells as compared with controls. Low levels of thrombin suppressed the maturation and secretion of cytokines in dendritic cells, but high levels enhanced this.
The effects of thrombin on allergic asthma are dose-dependent, with detrimental effects at high doses and protective effects at low doses. These data demonstrate that thrombin modulates the outcome in allergic bronchial asthma.
除了在凝血系统中的作用外，凝血酶还通过其蛋白酶激活受体（PAR）在炎症反应中发挥重要作用。然而，凝血酶在免疫反应中的作用尚不清楚。
评估凝血酶是否在变应性支气管哮喘中具有调节作用。
通过腹腔内致敏和卵清蛋白吸入挑战在小鼠中诱导支气管哮喘。在每次过敏原攻击前通过吸入给予凝血酶或其抑制剂。
具有低但持续的凝血激活的小鼠减少了过敏炎症，低剂量的凝血酶抑制了变应性哮喘，但高剂量的凝血酶使哮喘恶化。抗凝血酶、argatroban、水蛭素和抗血栓调节素抗体加重了变应性哮喘。同时抑制凝血酶和激活蛋白 C 的抑制剂水平较高的小鼠疾病更严重。PAR-1 杂合子小鼠的过敏炎症减少，但 PAR-1 激动剂使病情恶化。与对照组相比，接受过 PAR-1 激动剂处理的 Th2 细胞过继转移的小鼠的变应性支气管炎症加重。低水平的凝血酶抑制树突状细胞中细胞因子的成熟和分泌，但高水平增强了这种作用。
凝血酶对变应性支气管哮喘的影响呈剂量依赖性，高剂量时有有害作用，低剂量时有保护作用。这些数据表明凝血酶调节变应性支气管哮喘的结局。
