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

被引：11

作者：

Elshikha, Ahmed S. ^{[1
,2
]}

Abboud, Georges ^{[3
]}

Van der Meijden-Erkelens, Lonneke ^{[1
]}

Lu, Yuanqing ^{[1
]}

Chen, Mong-Jen ^{[1
]}

Yuan, Ye ^{[1
]}

Ponjee, Godelieva ^{[1
]}

Zeumer, Leilani ^{[3
]}

Satoh, Minoru ^{[4
]}

Morel, Laurence ^{[3
]}

Song, Sihong ^{[1
]}

机构：

[1] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 USA

[2] Zagazig Univ, Dept Pharmaceut, Zagazig 44519, Sharkia, Egypt

[3] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

[4] Univ Occupat & Environm Hlth, Dept Clin Nursing, Kitakyushu, Fukuoka 8078555, Japan

来源：

JOURNAL OF CLINICAL MEDICINE | 2019年 / 8卷 / 09期

关键词：

Lupus; Diffuse alveolar hemorrhage (DAH); alpha-1-antitrypsin (AAT); NECROSIS-FACTOR-ALPHA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; BONE LOSS; PULMONARY HEMORRHAGE; AUGMENTATION THERAPY; LYMPHOID-TISSUE; VIRAL SERPIN; I INTERFERON; MOUSE MODEL;

D O I：

10.3390/jcm8091341

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Ly6C(hi) 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.

引用

页数：16

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