Cargando…

L-Selectin Shedding Regulates Leukocyte Recruitment

The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration b...

Descripción completa

Detalles Bibliográficos
Autores principales: Hafezi-Moghadam, Ali, Thomas, Kennard L., Prorock, Alyson J., Huo, Yuqing, Ley, Klaus
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193368/
https://www.ncbi.nlm.nih.gov/pubmed/11283159
_version_ 1782147454409375744
author Hafezi-Moghadam, Ali
Thomas, Kennard L.
Prorock, Alyson J.
Huo, Yuqing
Ley, Klaus
author_facet Hafezi-Moghadam, Ali
Thomas, Kennard L.
Prorock, Alyson J.
Huo, Yuqing
Ley, Klaus
author_sort Hafezi-Moghadam, Ali
collection PubMed
description The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1–dependent mechanism. We examined the quality of leukocyte rolling and L-selectin–mediated signaling. Blockade of L-selectin shedding significantly reduced the “jerkiness” of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1–conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice.
format Text
id pubmed-2193368
institution National Center for Biotechnology Information
language English
publishDate 2001
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21933682008-04-22 L-Selectin Shedding Regulates Leukocyte Recruitment Hafezi-Moghadam, Ali Thomas, Kennard L. Prorock, Alyson J. Huo, Yuqing Ley, Klaus J Exp Med Original Article The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1–dependent mechanism. We examined the quality of leukocyte rolling and L-selectin–mediated signaling. Blockade of L-selectin shedding significantly reduced the “jerkiness” of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1–conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice. The Rockefeller University Press 2001-04-02 /pmc/articles/PMC2193368/ /pubmed/11283159 Text en © 2001 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 Original Article
Hafezi-Moghadam, Ali
Thomas, Kennard L.
Prorock, Alyson J.
Huo, Yuqing
Ley, Klaus
L-Selectin Shedding Regulates Leukocyte Recruitment
title L-Selectin Shedding Regulates Leukocyte Recruitment
title_full L-Selectin Shedding Regulates Leukocyte Recruitment
title_fullStr L-Selectin Shedding Regulates Leukocyte Recruitment
title_full_unstemmed L-Selectin Shedding Regulates Leukocyte Recruitment
title_short L-Selectin Shedding Regulates Leukocyte Recruitment
title_sort l-selectin shedding regulates leukocyte recruitment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193368/
https://www.ncbi.nlm.nih.gov/pubmed/11283159
work_keys_str_mv AT hafezimoghadamali lselectinsheddingregulatesleukocyterecruitment
AT thomaskennardl lselectinsheddingregulatesleukocyterecruitment
AT prorockalysonj lselectinsheddingregulatesleukocyterecruitment
AT huoyuqing lselectinsheddingregulatesleukocyterecruitment
AT leyklaus lselectinsheddingregulatesleukocyterecruitment