High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis. J Cell Mol Med 2016 Nov;20(11):2029-2035
Date
10/27/2016Pubmed ID
27295971Pubmed Central ID
PMC5082406DOI
10.1111/jcmm.12891Scopus ID
2-s2.0-84977483713 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Coagulation activation accompanied by reduced anticoagulant activity is a key characteristic of patients with idiopathic pulmonary fibrosis (IPF). Although the importance of coagulation activation in IPF is well studied, the potential relevance of endogenous anticoagulant activity in IPF progression remains elusive. We assess the importance of the endogenous anticoagulant protein C pathway on disease progression during bleomycin-induced pulmonary fibrosis. Wild-type mice and mice with high endogenous activated protein C APC levels (APChigh ) were subjected to bleomycin-induced pulmonary fibrosis. Fibrosis was assesses by hydroxyproline and histochemical analysis. Macrophage recruitment was assessed immunohistochemically. In vitro, macrophage migration was analysed by transwell migration assays. Fourteen days after bleomycin instillation, APChigh mice developed pulmonary fibrosis to a similar degree as wild-type mice. Interestingly, Aschcroft scores as well as lung hydroxyproline levels were significantly lower in APChigh mice than in wild-type mice on day 28. The reduction in fibrosis in APChigh mice was accompanied by reduced macrophage numbers in their lungs and subsequent in vitro experiments showed that APC inhibits thrombin-dependent macrophage migration. Our data suggest that high endogenous APC levels inhibit the progression of bleomycin-induced pulmonary fibrosis and that APC modifies pulmonary fibrosis by limiting thrombin-dependent macrophage recruitment.
Author List
Lin C, von der Thüsen J, Isermann B, Weiler H, van der Poll T, Borensztajn K, Spek CAMESH terms used to index this publication - Major topics in bold
AnimalsBleomycin
Disease Progression
Fibroblasts
Humans
Macrophages
Mice
Mice, Inbred C57BL
Monocytes
NIH 3T3 Cells
Protein C
Pulmonary Fibrosis
RAW 264.7 Cells
Thrombin
