Alpha-1-antitrypsin ameliorates pristane induced diffuse alveolar hemorrhage in mice

Ahmed S. Elshikha, Georges Abboud, Lonneke van der Meijden-Erkelens, Yuanqing Lu, Mong Jen Chen, Ye Yuan, Godelieva Ponjee, Leilani Zeumer, Minoru Satoh, Laurence Morel, Sihong Song

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number1341
JournalJournal of Clinical Medicine
Volume8
Issue number9
DOIs
StatePublished - Sep 2019
Externally publishedYes

Keywords

  • Alpha-1-antitrypsin (AAT)
  • Diffuse alveolar hemorrhage (DAH)
  • Lupus

ASJC Scopus subject areas

  • Medicine(all)

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