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High endogenous activated protein C levels attenuates bleomycin‐induced pulmonary fibrosis
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lin, Cong Thüsen, Jan H. Von Der Isermann, Berend Weiler, Hartmut Poll, Tom Van Der Borensztajn, Keren Spek, C. Arnold |
| Copyright Year | 2016 |
| Abstract | 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. |
| Starting Page | 2029 |
| Ending Page | 2035 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 27295971 |
| Alternate Webpage(s) | https://doi.org/10.1111/jcmm.12891 |
| DOI | 10.1111/jcmm.12891 |
| Journal | Journal of cellular and molecular medicine |
| Volume Number | 20 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anticoagulants Bleomycin Cell Migration Assays Disease Progression Hydroxyproline Idiopathic Pulmonary Fibrosis Instillation (procedure) Patients Structure of parenchyma of lung drotrecogin alfa |
| Content Type | Text |
| Resource Type | Article |
