Overexpression of activated protein C hampers bacterial dissemination during pneumococcal pneumonia

BMC Infectious Diseases

Tom van der Poll⁶  Cornelis van ’t Veer⁵  Berend Isermann¹  Hartmut Weiler⁴  Onno J de Boer³  Joost CM Meijers⁷  Joris JTH Roelofs³  Liesbeth M Kager²  Johannes Daan de Boer⁵ 

[1] Department of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke University, Magdeburg, Germany;Center for Experimental and Molecular Medicine (CEMM), Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, Amsterdam, 1105 AZ, The Netherlands;Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands;Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA;Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands;Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands;Department Plasma Proteins, Sanquin, Amsterdam, The Netherlands

关键词: Neutrophils;    Activated protein C;    Coagulation;    Inflammation;    Pneumonia;   

Others  :  1122129
DOI  :  10.1186/s12879-014-0559-3

 received in 2014-06-30, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

Background

During pneumonia, inflammation and coagulation are activated as part of anti-bacterial host defense. Activated protein C (APC) has anticoagulant and anti-inflammatory properties and until recently was a registered drug for the treatment of severe sepsis. Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia.

Methods

We aimed to investigate the effect of high APC levels during experimental pneumococcal pneumonia. Wild type (WT) and APC overexpressing (APC^high)-mice were intranasally infected with S. pneumoniae and sacrificed after 6, 24 or 48 hours, or followed in a survival study.

Results

In comparison to WT mice, APC^high-mice showed decreased bacterial dissemination to liver and spleen, while no differences in bacterial loads were detected at the primary site of infection. Although no differences in the extent of lung histopathology were seen, APC^high-mice showed a significantly decreased recruitment of neutrophils into lung tissue and bronchoalveolar lavage fluid. Activation of coagulation was not altered in APC^high-mice. No differences in survival were observed between WT and APC^high-mice (P =0.06).

Conclusion

APC overexpression improves host defense during experimental pneumococcal pneumonia. This knowledge may add to a better understanding of the regulation of the inflammatory and procoagulant responses during severe Gram-positive pneumonia.

【 授权许可】

   
2014 de Boer et al.; licensee BioMed Central Ltd.

【 图 表 】

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