Amnion Epithelial Cells Promote Lung Repair via Lipoxin A4. (7th November 2016)

• Record Type: Journal Article
• Authors: Tan, Jean L.; Tan, Yan Z.; Muljadi, Ruth; Chan, Siow T.; Lau, Sin N.; Mockler, Joanne C.; Wallace, Euan M.; Lim, Rebecca
• Is Part Of: Stem cells translational medicine. Volume 6:Number 4(2017)
• Page Start: 1085
• Page End: 1095
• Publication Date: 2016-11-07
• Subjects: Lipoxin A4 -- Lung fibrosis -- Inflammation -- Macrophages -- Neutrophils; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2016-0077
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Human amnion epithelial cells (hAECs) have been shown to possess potent immunomodulatory properties across a number of disease models. Recently, we reported that hAECs influence macrophage polarization and activity, and that this step was dependent on regulatory T cells. In this study, we aimed to assess the effects of hAEC-derived proresolution lipoxin-A4 (LXA4) on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury. Using C57Bl6 mice, we administered 4 million hAECs intraperitoneally 24 hours after bleomycin challenge. Outcomes were measured at days 3, 5, and 7. hAEC administration resulted in significant changes to T-cell, macrophage, dendritic cell, and monocyte/macrophage infiltration and phenotypes. Endogenous levels of lipoxygenases, LXA4, and the lipoxin receptor FPR2 were elevated in hAEC-treated animals. Furthermore, we showed that the effects of hAECs on macrophage phagocytic activity and T-cell suppression are LXA4 dependent, whereas the inhibition of neutrophil-derived myleoperoxidase by hAECs is independent of LXA4. This study provides the first evidence that lipid-based mediators contribute to the immunomodulatory effects of hAECs and further supports the growing body of evidence that LXA4 is proresolutionary in lung injury. This discovery of LXA4-dependent communication between hAECs, macrophages, T cells, and neutrophils is important to the understanding of hAEC biodynamics and would be expected to inform future clinical applications.