OK COBRE: NEUTROPHIL PROTEINASE-3 AUTOANTIGEN EXPRESSION AND REGULATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究总结 蛋白C途径成员在炎症和凝血的调节中起主要作用。内皮蛋白C受体(EPCR)是一种1型跨膜受体/辅因子蛋白，可加速活化蛋白C的生成，丝氨酸蛋白酶可抑制凝血和抑制炎症。循环可溶形式的EPCR(SEPCR)保留了与活化蛋白C的结合亲和力，并通过改变其大分子特异性来抑制这种丝氨酸蛋白酶的抗凝血活性。SEPCR还通过与表面表达的丝氨酸蛋白酶-3和对细胞黏附事件重要的β2整合素结合来与激活的中性粒细胞结合。 该项目的主要目标是确定支持sEPCR与中性粒细胞结合的分子模板，并确定sEPCR、PR3和β2整合素之间相互作用的功能后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Research Summary The protein C pathway members play a primary role in modulation of inflammation and coagulation. The endothelial protein C receptor (EPCR) is a type 1 transmembrane receptor/cofactor protein that accelerates generation of activated protein C, the serine proteinase that inhibits coagulation and limits inflammation. The circulating, soluble form of EPCR (sEPCR) retains binding affinity to activated protein C, and inhibits the anticoagulant activity of this serine proteinase by altering its macromolecular specificity. sEPCR also binds to activated neutrophils by binding to surface-expressed proteinase-3, also a serine proteinase, and a beta2 integrin, important for cell adhesion events. I. Primary objectives of the project were to identify the molecular template that supports sEPCR binding to neutrophils, and to identify the functional consequences of the interactions between sEPCR, PR3 and beta2 integrin.