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Protein C inhibitor - a novel antimicrobial agent
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2009 (English)In: PLoS Pathogens, ISSN 1553-7366, Vol. 5, no 12, e1000698- p.Article in journal (Refereed) Published
Abstract [en]

Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity.

Place, publisher, year, edition, pages
2009. Vol. 5, no 12, e1000698- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-112921DOI: 10.1371/journal.ppat.1000698ISI: 000274227000022PubMedID: 20019810OAI: oai:DiVA.org:uu-112921DiVA: diva2:288970
Available from: 2010-01-22 Created: 2010-01-22 Last updated: 2010-12-21Bibliographically approved

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