{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Elshikha AS"],"funding":["Grifols Inc.","Egypt Government Scholarship","University of Florida Foundation"],"pagination":["E1341"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6780888"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(9)"],"pubmed_abstract":["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-α 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 Ly6C<sup>hi</sup> 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."],"journal":["Journal of clinical medicine"],"pubmed_title":["Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice."],"pmcid":["PMC6780888"],"funding_grant_id":["89815","62632","71916"],"pubmed_authors":["van der Meijden-Erkelens L","Chen MJ","Lu Y","Abboud G","Elshikha AS","Ponjee G","Zeumer L","Song S","Morel L","Satoh M","Yuan Y"],"additional_accession":[]},"is_claimable":false,"name":"Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice.","description":"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-α 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 Ly6C<sup>hi</sup> 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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2026-05-06T23:00:33.635Z","creation":"2019-11-07T08:04:27Z"},"accession":"S-EPMC6780888","cross_references":{"pubmed":["31470606"],"doi":["10.3390/jcm8091341"]}}