Abstract |
Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, histidine-rich glycoprotein ( HRG), an abundant plasma protein, was found to kill S pyogenes. Furthermore, S pyogenes grew more efficiently in HRG-deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG-deficient mice were strikingly more susceptible to S pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation were diminished compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG-deficient mice, and they died earlier and with a significantly higher mortality rate than control animals. HRG-deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defense at the local site of bacterial infection.
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Authors | Oonagh Shannon, Victoria Rydengård, Artur Schmidtchen, Matthias Mörgelin, Per Alm, Ole E Sørensen, Lars Björck |
Journal | Blood
(Blood)
Vol. 116
Issue 13
Pg. 2365-72
(Sep 30 2010)
ISSN: 1528-0020 [Electronic] United States |
PMID | 20587784
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Proteins
- Proteins
- histidine-rich proteins
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Topics |
- Animals
- Blood Coagulation
(genetics, physiology)
- Blood Proteins
(deficiency, genetics, immunology, physiology)
- Disease Models, Animal
- Female
- Humans
- Immunity, Innate
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microscopy, Electron, Transmission
- Proteins
(genetics, immunology, pharmacology, physiology)
- Sepsis
(blood, immunology, microbiology)
- Streptococcal Infections
(blood, immunology, microbiology)
- Streptococcus pyogenes
(growth & development, immunology, pathogenicity)
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