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PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane

Platelet-endothelial cell adhesion molecule (PECAM)-1 has been implicated in leukocyte migration through the perivascular basement membrane (PBM) though the mechanisms involved are unclear. The present results demonstrate that the ability of α(6) integrins to mediate neutrophil migration through the...

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Autores principales: Dangerfield, John, Larbi, Karen Y., Huang, Miao-Tzu, Dewar, Ann, Nourshargh, Sussan
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194111/
https://www.ncbi.nlm.nih.gov/pubmed/12417630
http://dx.doi.org/10.1084/jem.20020324
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author Dangerfield, John
Larbi, Karen Y.
Huang, Miao-Tzu
Dewar, Ann
Nourshargh, Sussan
author_facet Dangerfield, John
Larbi, Karen Y.
Huang, Miao-Tzu
Dewar, Ann
Nourshargh, Sussan
author_sort Dangerfield, John
collection PubMed
description Platelet-endothelial cell adhesion molecule (PECAM)-1 has been implicated in leukocyte migration through the perivascular basement membrane (PBM) though the mechanisms involved are unclear. The present results demonstrate that the ability of α(6) integrins to mediate neutrophil migration through the PBM is PECAM-1 dependent, a response associated with PECAM-1–mediated increased expression of α(6)β(1) on transmigrating neutrophils in vivo. An anti-α(6) integrins mAb (GoH3) inhibited (78%, P < 0.001) neutrophil migration through interleukin (IL)-1β–stimulated cremasteric venules, primarily at the level of the PBM, as analyzed by intravital and electron microscopy. In PECAM-1–deficient mice (KO), a reduced level of neutrophil transmigration elicited by IL-1β (4-h reaction) was observed in both the cremaster muscle (55% inhibition, P < 0.05) and in the peritoneum (57% inhibition, P < 0.01) but GoH3 had no additional inhibitory effect on these responses. FACS(®) analysis of neutrophils demonstrated increased expression of α(6)β(1) on transmigrated peritoneal neutrophils, as compared with blood neutrophils, in wild-type but not KO mice even though neutrophils from both strains of mice exhibited comparable levels of intracellular expression of α(6) as observed by immunofluorescent staining and confocal microscopy. Furthermore, mice deficient in either leukocyte or endothelial cell PECAM-1, as developed by bone marrow transplantation, demonstrated a similar level of reduced neutrophil transmigration and expression of α(6)β(1) on transmigrated neutrophils as that detected in KO mice. The results demonstrate a role for PECAM-1 homophilic interaction in neutrophil transmigration and increased expression of α(6)β(1) on the cell surface of transmigrated neutrophils in vivo, a response that could contribute to the mechanism of PECAM-1–mediated neutrophil migration through the PBM.
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spelling pubmed-21941112008-04-11 PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane Dangerfield, John Larbi, Karen Y. Huang, Miao-Tzu Dewar, Ann Nourshargh, Sussan J Exp Med Article Platelet-endothelial cell adhesion molecule (PECAM)-1 has been implicated in leukocyte migration through the perivascular basement membrane (PBM) though the mechanisms involved are unclear. The present results demonstrate that the ability of α(6) integrins to mediate neutrophil migration through the PBM is PECAM-1 dependent, a response associated with PECAM-1–mediated increased expression of α(6)β(1) on transmigrating neutrophils in vivo. An anti-α(6) integrins mAb (GoH3) inhibited (78%, P < 0.001) neutrophil migration through interleukin (IL)-1β–stimulated cremasteric venules, primarily at the level of the PBM, as analyzed by intravital and electron microscopy. In PECAM-1–deficient mice (KO), a reduced level of neutrophil transmigration elicited by IL-1β (4-h reaction) was observed in both the cremaster muscle (55% inhibition, P < 0.05) and in the peritoneum (57% inhibition, P < 0.01) but GoH3 had no additional inhibitory effect on these responses. FACS(®) analysis of neutrophils demonstrated increased expression of α(6)β(1) on transmigrated peritoneal neutrophils, as compared with blood neutrophils, in wild-type but not KO mice even though neutrophils from both strains of mice exhibited comparable levels of intracellular expression of α(6) as observed by immunofluorescent staining and confocal microscopy. Furthermore, mice deficient in either leukocyte or endothelial cell PECAM-1, as developed by bone marrow transplantation, demonstrated a similar level of reduced neutrophil transmigration and expression of α(6)β(1) on transmigrated neutrophils as that detected in KO mice. The results demonstrate a role for PECAM-1 homophilic interaction in neutrophil transmigration and increased expression of α(6)β(1) on the cell surface of transmigrated neutrophils in vivo, a response that could contribute to the mechanism of PECAM-1–mediated neutrophil migration through the PBM. The Rockefeller University Press 2002-11-04 /pmc/articles/PMC2194111/ /pubmed/12417630 http://dx.doi.org/10.1084/jem.20020324 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Dangerfield, John
Larbi, Karen Y.
Huang, Miao-Tzu
Dewar, Ann
Nourshargh, Sussan
PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title_full PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title_fullStr PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title_full_unstemmed PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title_short PECAM-1 (CD31) Homophilic Interaction Up-Regulates α(6)β(1) on Transmigrated Neutrophils In Vivo and Plays a Functional Role in the Ability of α(6) Integrins to Mediate Leukocyte Migration through the Perivascular Basement Membrane
title_sort pecam-1 (cd31) homophilic interaction up-regulates α(6)β(1) on transmigrated neutrophils in vivo and plays a functional role in the ability of α(6) integrins to mediate leukocyte migration through the perivascular basement membrane
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194111/
https://www.ncbi.nlm.nih.gov/pubmed/12417630
http://dx.doi.org/10.1084/jem.20020324
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