Hart D A, Garlepp M, Fritzler M
Joint Injury and Diseases Research Group, University of Calgary Health Sciences Centre, Canada.
J Clin Lab Immunol. 1989 Sep;30(1):27-34.
Analysis of plasma proteinase during disease progression in murine models of systemic lupus erythematosus revealed three different patterns of regulation. Female NZB/W mice exhibited no age-dependent alterations in plasma proteinase activity from 3-9 months of age. Animals at nine months of age exhibited splenomegaly, high titers of serum autoantibodies and evidence of kidney disease, but no disruption of plasma proteinase activity. Male BxSB mice exhibited elevations in plasma proteinase activity as a late-onset (greater than 20 weeks of age) feature of the disease process. The onset of proteinase dysregulation occurred after significant mortality was evident and therefore variables associated with the induction of elevated levels of plasma proteinase activity are not related to early mortality factors. In contrast, female MRL-lpr mice exhibited age-dependent induction of elevated plasma proteinase activity which correlated temporally with the onset of mortality and the previously described reticuloendothelial system activation (Hart, J. Clin. Lab. Immunol., 26, 129). Interestingly, male MRL-lpr mice, which live slightly longer than female mice of the same strain, exhibited a delayed onset of plasma proteinase dysregulation. These results indicate that induction of changes in plasma proteinase regulation during the natural course of disease varies between these three murine models of SLE. Assessment of plasma proteinase regulation in human disease may reveal subpopulations of patients with features analogous to the murine models, which in turn could influence the choice of therapeutic modalities in disease management.
对系统性红斑狼疮小鼠模型疾病进展过程中血浆蛋白酶的分析揭示了三种不同的调节模式。雌性NZB/W小鼠在3至9月龄期间血浆蛋白酶活性未出现与年龄相关的变化。9月龄的动物出现脾肿大、高滴度血清自身抗体以及肾脏疾病迹象，但血浆蛋白酶活性未受破坏。雄性BxSB小鼠血浆蛋白酶活性升高，这是疾病进程的一种迟发性（大于20周龄）特征。蛋白酶调节异常在明显的高死亡率出现后才发生，因此与血浆蛋白酶活性升高诱导相关的变量与早期死亡因素无关。相比之下，雌性MRL-lpr小鼠血浆蛋白酶活性升高呈现年龄依赖性诱导，这与死亡率的开始以及先前描述的网状内皮系统激活在时间上相关（哈特，《临床实验室免疫学杂志》，26，129）。有趣的是，雄性MRL-lpr小鼠比同品系雌性小鼠寿命稍长，其血浆蛋白酶调节异常出现延迟。这些结果表明，在这三种系统性红斑狼疮小鼠模型中，疾病自然进程中血浆蛋白酶调节变化的诱导情况各不相同。对人类疾病中血浆蛋白酶调节的评估可能会揭示出具有与小鼠模型类似特征的患者亚群，这反过来可能会影响疾病管理中治疗方式的选择。
