Enzymology
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Researchers from University of Amsterdam report recent findings in protease
2007 NOV 19 -- Current study results from the report, 'Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation,' have been published. According to recent research published in the journal Blood, "Coagulation proteases may act as cell signaling molecules via protease-activated receptor (PAR) cleavage, subsequently affecting cellular and inflammatory responses. Activation of PARs in the setting of systemic inflammation and disseminated intravascular coagulation (DIC) might thus exacerbate the inflammatory response contributing to tissue and organ damage." "To investigate the role of PAR-4 in these processes, we subjected mice to a model of systemic inflammation and DIC (Shwartzman reaction) in the absence or presence of a cell-penetrating pepducin antagonist of PAR-4 (P4pal-10). P4pal-10 dose-dependently diminished the severity of endotoxemia and preserved liver, kidney, as well as lung function. Moreover, systemic inflammation and local (neutrophilic) inflammatory responses were attenuated. In vitro migration assays and P4pal-10 treatment in neutropenic mice suggest an essential role for neutrophils in PAR-4-mediated pathology. P4pal-10 treatment of thrombocytopenic mice excluded the involvement of platelets in this phenomenon," wrote S.H. Slofstra and colleagues, University of Amsterdam. The researchers concluded: "These results uncover an important role for PAR-4 in the Shwartzman reaction and suggest that inhibition of PAR-4 signaling in neutrophils could be protective in systemic inflammation and DIC." Slofstra and colleagues published their study in Blood (Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation. Blood, 2007;110(9):3176-82). For additional information, contact S.H. Slofstra, University of Amsterdam, Center for Experimental and Molecular Medicine, Academic Medical Center, Meibregdreef 9, 1105 AZ Amsterdam, Netherlands. The publisher's contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA. Keywords: Netherlands, Enzymology, Protease, Therapy, Treatment. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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