Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis

Blood. 2010 Sep 30;116(13):2365-72. doi: 10.1182/blood-2010-02-271858. Epub 2010 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation / genetics
  • Blood Coagulation / physiology
  • Blood Proteins / deficiency
  • Blood Proteins / genetics
  • Blood Proteins / immunology
  • Blood Proteins / physiology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity, Innate
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Proteins / genetics
  • Proteins / immunology
  • Proteins / pharmacology
  • Proteins / physiology*
  • Sepsis / blood*
  • Sepsis / immunology
  • Sepsis / microbiology*
  • Streptococcal Infections / blood*
  • Streptococcal Infections / immunology
  • Streptococcal Infections / microbiology*
  • Streptococcus pyogenes* / growth & development
  • Streptococcus pyogenes* / immunology
  • Streptococcus pyogenes* / pathogenicity


  • Blood Proteins
  • Proteins
  • histidine-rich proteins