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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193368/ https://www.ncbi.nlm.nih.gov/pubmed/11283159 |
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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 |
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