부산대학교 도서관

Both the complement system and tissue factor ( TF), a key initiating component of coagulation, are activated in sepsis, and cross-talk occurs between the complement and coagulation systems. C1-inhibitor ( C1- INH) can act as a regulator in both systems. Our aim in this study was to examine this cross-talk by investigating the effects of C1- INH on Escherichia coli-induced haemostasis and inflammation. Fresh human whole blood collected in lepirudin was incubated with E. coli or ultrapurified E. coli lipopolysaccharide ( LPS) in the absence or presence of C1- INH or protease-inactivated C1- INH. C3 activation was blocked by compstatin, a specific C3 convertase inhibitor. TF mRNA was measured using reverse transcription-quantitative polymerase chain reaction ( RT- qPCR), and TF surface expression was measured by flow cytometry. In plasma, the terminal complement complex, prothrombin F1·2 ( PTF1·2) and long pentraxin 3 ( PTX3) were measured by enzyme-linked immunosorbent assay ( ELISA). Cytokines were analysed using a multiplex kit. C1- INH (1·25-5 mg/ml) reduced both LPS- and E. coli-induced coagulation, measured as a reduction of PTF1·2 in plasma, efficiently and dose-dependently ( P < 0·05). Both LPS and E. coli induced marked up-regulation of TF mRNA levels and surface expression on whole blood monocytes. This up-regulation was reduced efficiently by treatment with C1- INH ( P < 0·05). C1- INH reduced the release of PTX3 ( P < 0·05) and virtually all cytokines measured ( P < 0·05). Complement activation was inhibited more efficiently with compstatin than with C1- INH. C1- INH inhibited most of the other readouts more efficiently, consistent with additional non-complement-dependent effects. These results indicate that complement plays a role in activating coagulation during sepsis and that C1- INH is a broad-spectrum attenuator of the inflammatory and haemostatic responses. [ABSTRACT FROM AUTHOR]