The effect of human amnion epithelial cells on lung development and inflammation in preterm lambs exposed to antenatal inflammation
- Papagianis, Paris, Ahmadi-Noorbakhsh, Siavash, Lim, Rebecca, Wallace, Euan, Polglase, Graeme, Pillow, J. Jane, Moss, Timothy
- Authors: Papagianis, Paris , Ahmadi-Noorbakhsh, Siavash , Lim, Rebecca , Wallace, Euan , Polglase, Graeme , Pillow, J. Jane , Moss, Timothy
- Date: 2021
- Type: Text , Journal article
- Relation: PloS one Vol. 16, no. 6 (2021), p. e0253456-e0253456
- Full Text:
- Reviewed:
- Description: Lung inflammation and impaired alveolarization are hallmarks of bronchopulmonary dysplasia (BPD). We hypothesize that human amnion epithelial cells (hAECs) are anti-inflammatory and reduce lung injury in preterm lambs born after antenatal exposure to inflammation. Pregnant ewes received either intra-amniotic lipopolysaccharide (LPS, from E.coli 055:B5 4mg) or saline (Sal) on day 126 of gestation. Lambs were delivered by cesarean section at 128 d gestation (term ~150 d). Lambs received intravenous hAECs (LPS/hAECs: n = 7 30x10.sup.6 cells) or equivalent volumes of saline (LPS/Sal, n = 10 or Sal/Sal, n = 9) immediately after birth. Respiratory support was gradually de-escalated, aimed at early weaning from mechanical ventilation towards unassisted respiration. Lung tissue was collected 1 week after birth. Lung morphology was assessed and mRNA levels for inflammatory mediators were measured. Respiratory support required by LPS/hAEC lambs was not different to Sal/Sal or LPS/Sal lambs. Lung tissue:airspace ratio was lower in the LPS/Sal compared to Sal/Sal lambs (P<0.05), but not LPS/hAEC lambs. LPS/hAEC lambs tended to have increased septation in their lungs versus LPS/Sal (P = 0.08). Expression of inflammatory cytokines was highest in LPS/hAECs lambs. Postnatal administration of a single dose of hAECs stimulates a pulmonary immune response without changing ventilator requirements in preterm lambs born after intrauterine inflammation.
- Authors: Papagianis, Paris , Ahmadi-Noorbakhsh, Siavash , Lim, Rebecca , Wallace, Euan , Polglase, Graeme , Pillow, J. Jane , Moss, Timothy
- Date: 2021
- Type: Text , Journal article
- Relation: PloS one Vol. 16, no. 6 (2021), p. e0253456-e0253456
- Full Text:
- Reviewed:
- Description: Lung inflammation and impaired alveolarization are hallmarks of bronchopulmonary dysplasia (BPD). We hypothesize that human amnion epithelial cells (hAECs) are anti-inflammatory and reduce lung injury in preterm lambs born after antenatal exposure to inflammation. Pregnant ewes received either intra-amniotic lipopolysaccharide (LPS, from E.coli 055:B5 4mg) or saline (Sal) on day 126 of gestation. Lambs were delivered by cesarean section at 128 d gestation (term ~150 d). Lambs received intravenous hAECs (LPS/hAECs: n = 7 30x10.sup.6 cells) or equivalent volumes of saline (LPS/Sal, n = 10 or Sal/Sal, n = 9) immediately after birth. Respiratory support was gradually de-escalated, aimed at early weaning from mechanical ventilation towards unassisted respiration. Lung tissue was collected 1 week after birth. Lung morphology was assessed and mRNA levels for inflammatory mediators were measured. Respiratory support required by LPS/hAEC lambs was not different to Sal/Sal or LPS/Sal lambs. Lung tissue:airspace ratio was lower in the LPS/Sal compared to Sal/Sal lambs (P<0.05), but not LPS/hAEC lambs. LPS/hAEC lambs tended to have increased septation in their lungs versus LPS/Sal (P = 0.08). Expression of inflammatory cytokines was highest in LPS/hAECs lambs. Postnatal administration of a single dose of hAECs stimulates a pulmonary immune response without changing ventilator requirements in preterm lambs born after intrauterine inflammation.
Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice
- Liong, Stella, Oseghale, Osezua, To, Eunice, Brassington, Kurt, Erlich, Jonathan, Luong, Raymond, Liong, Felicia, Brooks, Robert, Martin, Cara, O'Toole, Sharon, Vinh, Antony, O'Neill, Luke, Bozinovski, Steven, Vlahos, Ross, Papagianis, Paris, O'Leary, John, Brooks, Doug, Selemidis, Stavros
- Authors: Liong, Stella , Oseghale, Osezua , To, Eunice , Brassington, Kurt , Erlich, Jonathan , Luong, Raymond , Liong, Felicia , Brooks, Robert , Martin, Cara , O'Toole, Sharon , Vinh, Antony , O'Neill, Luke , Bozinovski, Steven , Vlahos, Ross , Papagianis, Paris , O'Leary, John , Brooks, Doug , Selemidis, Stavros
- Date: 2020
- Type: Text , Journal article
- Relation: Proceedings of the National Academy of Sciences of the United States of America Vol. 117, no. 40 (2020), p. 24964-24973
- Full Text:
- Reviewed:
- Description: Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy. © 2020 National Academy of Sciences. All rights reserved.
- Authors: Liong, Stella , Oseghale, Osezua , To, Eunice , Brassington, Kurt , Erlich, Jonathan , Luong, Raymond , Liong, Felicia , Brooks, Robert , Martin, Cara , O'Toole, Sharon , Vinh, Antony , O'Neill, Luke , Bozinovski, Steven , Vlahos, Ross , Papagianis, Paris , O'Leary, John , Brooks, Doug , Selemidis, Stavros
- Date: 2020
- Type: Text , Journal article
- Relation: Proceedings of the National Academy of Sciences of the United States of America Vol. 117, no. 40 (2020), p. 24964-24973
- Full Text:
- Reviewed:
- Description: Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy. © 2020 National Academy of Sciences. All rights reserved.
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