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Endothelial cells of pulmonary origin display unique sensitivity to the bacterial endotoxin lipopolysaccharide. / Morsing, Sofia K. H.; Zeeuw van der Laan, Eveline; van Stalborch, Anne-Marieke D.; van Buul, Jaap D.; Vlaar, Alexander P. J.; Kapur, Rick.

In: Physiological reports, Vol. 10, No. 8, e15271, 01.04.2022, p. e15271.

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@article{4f2ff99132a54766943b21ef78905b3a,
title = "Endothelial cells of pulmonary origin display unique sensitivity to the bacterial endotoxin lipopolysaccharide",
abstract = "Acute respiratory distress syndrome (ARDS) is a major clinical problem without available therapies. Known risks for ARDS include severe sepsis, SARS-CoV-2, gram-negative bacteria, trauma, pancreatitis, and blood transfusion. During ARDS, blood fluids and inflammatory cells enter the alveoli, preventing oxygen exchange from air into blood vessels. Reduced pulmonary endothelial barrier function, resulting in leakage of plasma from blood vessels, is one of the major determinants in ARDS. It is, however, unknown why systemic inflammation particularly targets the pulmonary endothelium, as endothelial cells (ECs) line all vessels in the vascular system of the body. In this study, we examined ECs of pulmonary, umbilical, renal, pancreatic, and cardiac origin for upregulation of adhesion molecules, ability to facilitate neutrophil (PMN) trans-endothelial migration (TEM) and for endothelial barrier function, in response to the gram-negative bacterial endotoxin LPS. Interestingly, we found that upon LPS stimulation, pulmonary ECs showed increased levels of adhesion molecules, facilitated more PMN-TEM and significantly perturbed the endothelial barrier, compared to other types of ECs. These observations could partly be explained by a higher expression of the adhesion molecule ICAM-1 on the pulmonary endothelial surface compared to other ECs. Moreover, we identified an increased expression of Cadherin-13 in pulmonary ECs, for which we demonstrated that it aids PMN-TEM in pulmonary ECs stimulated with LPS. We conclude that pulmonary ECs are uniquely sensitive to LPS, and intrinsically different, compared to ECs from other vascular beds. This may add to our understanding of the development of ARDS upon systemic inflammation.",
keywords = "ARDS, LPS, TRALI, endothelial cells",
author = "Morsing, {Sofia K. H.} and {Zeeuw van der Laan}, Eveline and {van Stalborch}, {Anne-Marieke D.} and {van Buul}, {Jaap D.} and Vlaar, {Alexander P. J.} and Rick Kapur",
note = "Funding Information: This work was supported by Sanquin PPOC grant 1808 (RK), ZonMW NWO Vici grant 91819632 (JDvB) and ZonMW NWO Vidi grant 09150172010047 (APJV). Funding Information: This work was supported by Sanquin PPOC grant 1808 (RK),?ZonMW NWO Vici grant 91819632 (JDvB) and ZonMW NWO Vidi grant 09150172010047 (APJV). Publisher Copyright: {\textcopyright} 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.",
year = "2022",
month = apr,
day = "1",
doi = "10.14814/phy2.15271",
language = "English",
volume = "10",
pages = "e15271",
journal = "Physiological reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Endothelial cells of pulmonary origin display unique sensitivity to the bacterial endotoxin lipopolysaccharide

AU - Morsing, Sofia K. H.

AU - Zeeuw van der Laan, Eveline

AU - van Stalborch, Anne-Marieke D.

AU - van Buul, Jaap D.

AU - Vlaar, Alexander P. J.

AU - Kapur, Rick

N1 - Funding Information: This work was supported by Sanquin PPOC grant 1808 (RK), ZonMW NWO Vici grant 91819632 (JDvB) and ZonMW NWO Vidi grant 09150172010047 (APJV). Funding Information: This work was supported by Sanquin PPOC grant 1808 (RK),?ZonMW NWO Vici grant 91819632 (JDvB) and ZonMW NWO Vidi grant 09150172010047 (APJV). Publisher Copyright: © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Acute respiratory distress syndrome (ARDS) is a major clinical problem without available therapies. Known risks for ARDS include severe sepsis, SARS-CoV-2, gram-negative bacteria, trauma, pancreatitis, and blood transfusion. During ARDS, blood fluids and inflammatory cells enter the alveoli, preventing oxygen exchange from air into blood vessels. Reduced pulmonary endothelial barrier function, resulting in leakage of plasma from blood vessels, is one of the major determinants in ARDS. It is, however, unknown why systemic inflammation particularly targets the pulmonary endothelium, as endothelial cells (ECs) line all vessels in the vascular system of the body. In this study, we examined ECs of pulmonary, umbilical, renal, pancreatic, and cardiac origin for upregulation of adhesion molecules, ability to facilitate neutrophil (PMN) trans-endothelial migration (TEM) and for endothelial barrier function, in response to the gram-negative bacterial endotoxin LPS. Interestingly, we found that upon LPS stimulation, pulmonary ECs showed increased levels of adhesion molecules, facilitated more PMN-TEM and significantly perturbed the endothelial barrier, compared to other types of ECs. These observations could partly be explained by a higher expression of the adhesion molecule ICAM-1 on the pulmonary endothelial surface compared to other ECs. Moreover, we identified an increased expression of Cadherin-13 in pulmonary ECs, for which we demonstrated that it aids PMN-TEM in pulmonary ECs stimulated with LPS. We conclude that pulmonary ECs are uniquely sensitive to LPS, and intrinsically different, compared to ECs from other vascular beds. This may add to our understanding of the development of ARDS upon systemic inflammation.

AB - Acute respiratory distress syndrome (ARDS) is a major clinical problem without available therapies. Known risks for ARDS include severe sepsis, SARS-CoV-2, gram-negative bacteria, trauma, pancreatitis, and blood transfusion. During ARDS, blood fluids and inflammatory cells enter the alveoli, preventing oxygen exchange from air into blood vessels. Reduced pulmonary endothelial barrier function, resulting in leakage of plasma from blood vessels, is one of the major determinants in ARDS. It is, however, unknown why systemic inflammation particularly targets the pulmonary endothelium, as endothelial cells (ECs) line all vessels in the vascular system of the body. In this study, we examined ECs of pulmonary, umbilical, renal, pancreatic, and cardiac origin for upregulation of adhesion molecules, ability to facilitate neutrophil (PMN) trans-endothelial migration (TEM) and for endothelial barrier function, in response to the gram-negative bacterial endotoxin LPS. Interestingly, we found that upon LPS stimulation, pulmonary ECs showed increased levels of adhesion molecules, facilitated more PMN-TEM and significantly perturbed the endothelial barrier, compared to other types of ECs. These observations could partly be explained by a higher expression of the adhesion molecule ICAM-1 on the pulmonary endothelial surface compared to other ECs. Moreover, we identified an increased expression of Cadherin-13 in pulmonary ECs, for which we demonstrated that it aids PMN-TEM in pulmonary ECs stimulated with LPS. We conclude that pulmonary ECs are uniquely sensitive to LPS, and intrinsically different, compared to ECs from other vascular beds. This may add to our understanding of the development of ARDS upon systemic inflammation.

KW - ARDS

KW - LPS

KW - TRALI

KW - endothelial cells

UR - http://www.scopus.com/inward/record.url?scp=85128501840&partnerID=8YFLogxK

U2 - 10.14814/phy2.15271

DO - 10.14814/phy2.15271

M3 - Article

C2 - 35439361

VL - 10

SP - e15271

JO - Physiological reports

JF - Physiological reports

SN - 2051-817X

IS - 8

M1 - e15271

ER -

ID: 23217698