OK COBRE: NEUTROPHIL PROTEINASE-3 AUTOANTIGEN EXPRESSION AND REGULATION

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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.