Gram-negative
sepsis is associated with
disseminated intravascular coagulation (
DIC) due to endothelial damage, which is induced by inflammatory mediators released from phagocytes activated by
lipopolysaccharide (LPS).
DIC is a systemic hemorrhagic syndrome, which results from the consumption of
coagulation factors for the formation of multiple thrombi in the systemic microvessels; it is associated with
multiple organ failure. Therefore, not only the systemic activation of coagulation but also the inflammatory response has been perceived as the therapeutic target for
DIC in
sepsis. We gave attention that
protein C inhibitor (PCI) acts as an inhibitor of both
plasma kallikrein and
thrombin, which are known to act not only as procoagulant
proteases but also as
chemotactic factors toward phagocytes. Then, we hypothesized that PCI possibly acts as an anti-
DIC agent rather than an inhibitor of the
protein C anticoagulant pathway under the pathophysiology of
DIC, accompanied by the decrease in the
thrombomodulin expression on endothelial cells. Our studies have suggested that PCI purified from human urine (uPCI) improves the pathophysiology of
DIC through the inhibition of activities of
plasma kallikrein and
thrombin, and the activities of PCI are regulated by N-
glycans. This review introduces the anti-
DIC action of PCI and about the modification of N-glycosylation site(s) of PCI to heighten the value of PCI as an anti-
DIC agent.