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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.

Author information

1
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
2
Department of Pharmaceutics, Zagazig University, Zagazig, Sharkia 44519, Egypt.
3
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
4
Department of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan.
5
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. shsong@cop.ufl.edu.

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 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.

KEYWORDS:

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

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