Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients
Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.535147/full |
| _version_ | 1818852882557960192 |
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| author | Vanessa Araujo Gomes Santaterra Maiara Marx Luz Fiusa Bidossessi Wilfried Hounkpe Francine Chenou Wouitchekpo Vincent Tonasse Loredana Nilkenes Gomes da Costa Loredana Nilkenes Gomes da Costa Diego Garcia-Weber Igor de Farias Domingos Igor de Farias Domingos Franciele de Lima Ivanio Teixeira Borba-Junior Aderson da Silva Araújo Antonio Roberto Lucena-Araújo Marcos André Cavalcante Bezerra Magnun Nueldo Nunes dos Santos Fernando Ferreira Costa Fernando Ferreira Costa Jaime Millán Erich Vinicius De Paula Erich Vinicius De Paula |
| author_facet | Vanessa Araujo Gomes Santaterra Maiara Marx Luz Fiusa Bidossessi Wilfried Hounkpe Francine Chenou Wouitchekpo Vincent Tonasse Loredana Nilkenes Gomes da Costa Loredana Nilkenes Gomes da Costa Diego Garcia-Weber Igor de Farias Domingos Igor de Farias Domingos Franciele de Lima Ivanio Teixeira Borba-Junior Aderson da Silva Araújo Antonio Roberto Lucena-Araújo Marcos André Cavalcante Bezerra Magnun Nueldo Nunes dos Santos Fernando Ferreira Costa Fernando Ferreira Costa Jaime Millán Erich Vinicius De Paula Erich Vinicius De Paula |
| author_sort | Vanessa Araujo Gomes Santaterra |
| collection | DOAJ |
| description | Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions. |
| first_indexed | 2024-12-19T07:27:59Z |
| format | Article |
| id | doaj.art-68ef82d31e9d4903aea19036d7c741a4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T07:27:59Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-68ef82d31e9d4903aea19036d7c741a42022-12-21T20:30:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.535147535147Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease PatientsVanessa Araujo Gomes Santaterra0Maiara Marx Luz Fiusa1Bidossessi Wilfried Hounkpe2Francine Chenou3Wouitchekpo Vincent Tonasse4Loredana Nilkenes Gomes da Costa5Loredana Nilkenes Gomes da Costa6Diego Garcia-Weber7Igor de Farias Domingos8Igor de Farias Domingos9Franciele de Lima10Ivanio Teixeira Borba-Junior11Aderson da Silva Araújo12Antonio Roberto Lucena-Araújo13Marcos André Cavalcante Bezerra14Magnun Nueldo Nunes dos Santos15Fernando Ferreira Costa16Fernando Ferreira Costa17Jaime Millán18Erich Vinicius De Paula19Erich Vinicius De Paula20School of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilDepartment of Biomedicine, Federal University of Piaui, Parnaiba, BrazilCentro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Madrid, SpainGenetics Postgraduate Program, Federal University of Pernambuco, Recife, BrazilDepartment of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilDepartment of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco (HEMOPE), Recife, BrazilGenetics Postgraduate Program, Federal University of Pernambuco, Recife, BrazilGenetics Postgraduate Program, Federal University of Pernambuco, Recife, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilSchool of Medical Sciences, University of Campinas, Campinas, BrazilHematology and Hemotherapy Center, University of Campinas, Campinas, BrazilCentro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Madrid, SpainSchool of Medical Sciences, University of Campinas, Campinas, BrazilHematology and Hemotherapy Center, University of Campinas, Campinas, BrazilFree extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.https://www.frontiersin.org/articles/10.3389/fimmu.2020.535147/fullendothelial barrierhemesickle cell diseaseelectric cell-substrate impedance sensingdanger-associated molecular patternhemopexin |
| spellingShingle | Vanessa Araujo Gomes Santaterra Maiara Marx Luz Fiusa Bidossessi Wilfried Hounkpe Francine Chenou Wouitchekpo Vincent Tonasse Loredana Nilkenes Gomes da Costa Loredana Nilkenes Gomes da Costa Diego Garcia-Weber Igor de Farias Domingos Igor de Farias Domingos Franciele de Lima Ivanio Teixeira Borba-Junior Aderson da Silva Araújo Antonio Roberto Lucena-Araújo Marcos André Cavalcante Bezerra Magnun Nueldo Nunes dos Santos Fernando Ferreira Costa Fernando Ferreira Costa Jaime Millán Erich Vinicius De Paula Erich Vinicius De Paula Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients Frontiers in Immunology endothelial barrier heme sickle cell disease electric cell-substrate impedance sensing danger-associated molecular pattern hemopexin |
| title | Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients |
| title_full | Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients |
| title_fullStr | Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients |
| title_full_unstemmed | Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients |
| title_short | Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients |
| title_sort | endothelial barrier integrity is disrupted in vitro by heme and by serum from sickle cell disease patients |
| topic | endothelial barrier heme sickle cell disease electric cell-substrate impedance sensing danger-associated molecular pattern hemopexin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.535147/full |
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