期刊
THROMBOSIS AND HAEMOSTASIS
卷 109, 期 4, 页码 726-737出版社
GEORG THIEME VERLAG KG
DOI: 10.1160/TH12-11-0859
关键词
Tuberculosis; inflammation; activated protein C; endothelial protein C receptor; lung; mice; infection
资金
- ZonMW [92003504]
- Stichting BeGeTu
- Mr. Willem Bakhuys Roozeboom Stichting
- Dutch Kidney Foundation [C09.2287]
- Dutch Thrombosis Foundation [TSN 2005-1]
The protein C (PC) system is an important regulator of both coagulation and inflammation. Activated PC (APC), together with its receptor the endothelial protein C receptor (EPCR), has anticoagulant and anti-inflammatory properties. During tuberculosis (TB), a devastating chronic pulmonary disease caused by Mycobacterium (M.) tuberculosis, both a local inflammatory reaction characterised by the recruitment of mainly mononuclear cells and the formation of pulmonary granulomas as well as activation of coagulation occurs as part of the host immune response. We investigated the role of EPCR and APC in a mouse model of TB using mice overexpressing EPCR (Tie2-EPCR), mice deficient for EPCR (EPCR-/-), mice treated with APC-inhibiting antibodies and mice overexpressing APC (APC(high)) and compared them with wild-type (WT) mice. Blood and organs were harvested to quantify bacterial loads, cellular influxes, cytokines, histopathology and coagulation parameters. Additionally observation studies were performed. Lung EPCR expression was upregulated during experimental TB. No significant differences in bacterial growth were seen between WT and Tie2-EPCR mice. However, Tie2-EPCR mice had decreased pulmonary coagulation activation, displayed an increased influx of macrophages 2 and 6 weeks after infection, but no increase in other proinflammatory markers. On the other hand, in EPCR-/--mice coagulation, activation was decreased 6 weeks post-infection, with little impact on other inflammation markers. APC-overexpression or treatment with anti-(A)PC antibodies displayed minimal effects during experimental, TB. In conclusion, EPCR and APC play a limited role in the host response during experimental pulmonary TB.
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