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J Clin Med. 2019 Aug 29;8(9). pii: E1341. doi: 10.3390/jcm8091341.

Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice.

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Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Department of Pharmaceutics, Zagazig University, Zagazig, Sharkia 44519, Egypt.
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
Department of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan.
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.


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 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.


Diffuse alveolar hemorrhage (DAH); Lupus; alpha-1-antitrypsin (AAT)

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