Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice
| Autor: | Yuanqing Lu, Mong-Jen Chen, Ye Yuan, Georges Abboud, Minoru Satoh, Ahmed S. Elshikha, Sihong Song, Laurence Morel, Leilani Zeumer, Lonneke van der Meijden-Erkelens, Godelieva Ponjee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Myeloid medicine.medical_treatment Transgene Intraperitoneal injection Alpha (ethology) lcsh:Medicine Lupus Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine IL-2 receptor 030304 developmental biology 0303 health sciences Systemic lupus erythematosus business.industry Pristane lcsh:R Diffuse alveolar hemorrhage General Medicine medicine.disease Endocrinology medicine.anatomical_structure chemistry alpha-1-antitrypsin (AAT) 030220 oncology & carcinogenesis Diffuse alveolar hemorrhage (DAH) business |
| Zdroj: | Journal of Clinical Medicine Volume 8 Issue 9 Journal of Clinical Medicine, Vol 8, Iss 9, p 1341 (2019) |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm8091341 |
| Popis: | Diffuse alveolar hemorrhage (DAH) is a fatal complication in patients with lupus. DAH can be induced in B6 mice by an intraperitoneal injection of pristane. Since human alpha-1-antitrypsin (hAAT) is an anti-inflammatory and immuno-regulatory protein, we investigated the protective effect of hAAT against pristane-induced DAH in B6 mice and hAAT transgenic (hAAT-Tg) mice. We first showed that hAAT Tg expression lowers TNF-&alpha production in B cells, as well as CD4+ T cells in untreated mice. Conversely, the frequency of regulatory CD4+CD25+ and CD4+CD25-IL-10+ cells was significantly higher in hAAT-Tg than in B6 mice. This confirmed the anti-inflammatory effect of hAAT that was observed even at steady state. One week after a pristane injection, the frequency of peritoneal Ly6Chi inflammatory monocytes and neutrophils in hAAT-Tg mice was significantly lower than that in B6 mice. Importantly, pristane-induced DAH was completely prevented in hAAT-Tg mice and this was associated with a modulation of anti- to pro-inflammatory myeloid cell ratio/balance. We also showed that treatment with hAAT decreased the severity of DAH in B6 mice. These results showed for the first time that hAAT has a therapeutic potential for the treatment of DAH. |
| Databáze: | OpenAIRE |
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