The cytoprotective effects of endogenous activated protein C reduce activation of coagulation during murine pneumococcal pneumonia and sepsis

Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and sepsis. Activated protein C (APC) has been implicated as an important anticoagulant and anti-inflammatory mediator. We here sought to determine the role of the anticoagulant and cytoprotective fun...

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Vydané v:Thrombosis research Ročník 135; číslo 3; s. 537 - 543
Hlavní autori: Schouten, Marcel, van ‘t Veer, Cornelis, Poulussen, Nadia, Meijers, Joost C.M., Levi, Marcel, Esmon, Charles T., van der Poll, Tom
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Elsevier Ltd 01.03.2015
Predmet:
Animals
Anticoagulants - metabolism
Blood Coagulation
coagulation
Cryoprotective Agents - metabolism
Enzyme Activation
Hematology, Oncology and Palliative Medicine
inflammation
Male
Mice
Mice, Inbred C57BL
pneumonia
Pneumonia, Pneumococcal - blood
Pneumonia, Pneumococcal - complications
Pneumonia, Pneumococcal - diagnosis
Pneumonia, Pneumococcal - metabolism
protein C
Protein C - metabolism
S. pneumoniae
sepsis
Sepsis - blood
Sepsis - complications
Sepsis - diagnosis
Sepsis - metabolism
Streptococcus pneumoniae - isolation & purification
S. pneumoniae
protein C
pneumonia
inflammation
coagulation
sepsis
ISSN:0049-3848, 1879-2472, 1879-2472
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Shrnutí:Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and sepsis. Activated protein C (APC) has been implicated as an important anticoagulant and anti-inflammatory mediator. We here sought to determine the role of the anticoagulant and cytoprotective functions of endogenous APC during pneumonia and sepsis caused by S. pneumoniae. Mice were treated intraperitoneally with monoclonal antibody (mAb) 1609 (which inhibits both anticoagulant and cytoprotective effects of APC), mAb 1591 (which inhibits only the anticoagulant effects of APC) or a control antibody mAb prior to infection with viable S. pneumoniae via the airways (to induce pneumonia) or via the tail vein (to induce primary sepsis). Mice were analyzed at 24 or 48hours after infection. mAb 1609, but not mAb 1591, enhanced the procoagulant response to pneumococcal pneumonia and sepsis, as indicated by elevated levels of thrombin-antithrombin complexes and D-dimer in plasma and lungs. mAb 1609 only modestly affected the fibrinolytic response (elevated plasma and lung levels of the fibrinolysis inhibitor plasminogen activator inhibitor type I during sepsis) and cytokine release (elevated plasma interleukin-6 concentrations during pneumonia). The cytoprotective effects of endogenous APC reduce activation of coagulation during murine pneumococcal pneumonia and sepsis. •Endogenous PC inhibits pulmonary and systemic coagulation in pneumococcal infection.•The cytoprotective effects of APC inhibit coagulation in pneumococcal infection.•Endogenous APC has small impact on fibrinolysis in pneumococcal infection.•Endogenous APC has small impact on inflammation in pneumococcal infection.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0049-3848
1879-2472
1879-2472
DOI:10.1016/j.thromres.2014.12.020