Impaired fibrinolysis and complement activation in Systemic Lupus Erythematosus contributes to disease amplification including increased risk of thrombosis and tissue Ischemia/Reperfusion (IR) injury. Previous work has demonstrated complement is a key regulator of tissue injury. In these studies inhibitors had varying efficacies in attenuating injury at primary versus systemic sites, such as lung. In this study the role of coagulation factors in tissue injury and complement function was evaluated. Tissue Factor Pathway Inhibitor (TFPI), an extrinsic pathway inhibitor, and Anti-Thrombin III, the downstream common pathway inhibitor, were utilized in this study. TFPI was more effective in attenuated primary intestinal tissue injury. However both attenuated systemic lung injury. However, ATIII treatment resulting in enhanced degradation of C3 split products in lung tissue compared to TFPI. This work delineates the influence of specific early and late coagulation pathway components during initial tissue injury versus later distal systemic tissue injury mechanism.

全身性红斑狼疮的纤维蛋白溶解受损和补体激活导致疾病扩大，包括血栓形成和组织缺血/再灌注（IR）损伤的风险增加。先前的工作表明补体是组织损伤的关键调节剂。在这些研究中，抑制剂在减轻主要部位和全身部位（例如肺部）的损伤方面具有不同的功效。在这项研究中，评估了凝血因子在组织损伤和补体功能中的作用。在本研究中，使用了组织因子途径抑制剂（TFPI）（一种外在途径抑制剂）和抗凝血酶III（一种下游通用途径抑制剂）。TFPI在减轻原发性肠组织损伤方面更有效。然而，两者均减轻了全身性肺损伤。然而，与TFPI相比，ATIII处理导致肺组织中C3分裂产物的降解增强。这项工作描述了在最初的组织损伤与以后的远端全身性组织损伤机制之间特定的早期和晚期凝血途径成分的影响。