Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration

Chemoattractant sensing, adhesiveness, and migration are critical events underlying the recruitment of neutrophils (PMNs) to sites of inflammation or infection. Defects in leukocyte adhesion or migration result in immunodeficiency disorders characterized by recurrent infections. In this study, we ev...

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Main Authors: Jouda Gamara, Lynn Davis, Emmanuelle Rollet-Labelle, Tsunaki Hongu, Yuji Funakoshi, Yasunori Kanaho, Fawzi Aoudjit, Sylvain G. Bourgoin
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/2713074
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author Jouda Gamara
Lynn Davis
Emmanuelle Rollet-Labelle
Tsunaki Hongu
Yuji Funakoshi
Yasunori Kanaho
Fawzi Aoudjit
Sylvain G. Bourgoin
author_facet Jouda Gamara
Lynn Davis
Emmanuelle Rollet-Labelle
Tsunaki Hongu
Yuji Funakoshi
Yasunori Kanaho
Fawzi Aoudjit
Sylvain G. Bourgoin
author_sort Jouda Gamara
collection DOAJ
description Chemoattractant sensing, adhesiveness, and migration are critical events underlying the recruitment of neutrophils (PMNs) to sites of inflammation or infection. Defects in leukocyte adhesion or migration result in immunodeficiency disorders characterized by recurrent infections. In this study, we evaluated the role of Arf6 on PMN adhesion in vitro and on migration to inflammatory sites using PMN-Arf6 conditional knockout (cKO) mice. In PMN-like PLB-985 silenced for Arf6 fMLP-mediated adhesion to the β2 integrin ligands, ICAM-1 and fibrinogen or the β1/β2 integrin ligand fibronectin was significantly reduced. Furthermore, overexpression of wild-type Arf6 promoted basal and fMLP-induced adhesion to immobilized integrin ligands, while overexpression of the dominant-negative Arf6 has the opposite effects. Using the Elane-Cre deleting mouse strains, we report that the level of Arf6 deletion in inflammatory PMNs isolated from the dorsal air pouches was stronger when compared to naïve cells isolated from the bone marrow. In PMN-Arf6 cKO mice, the recruitment of PMNs into the dorsal air pouch injected with LPS or the chemoattractant fMLP was significantly diminished. Impaired cell migration correlated with reduced cell surface expression of CD11a and CD11b in Arf6 cKO PMNs. Our results highlight that Arf6 regulates the activity and possibly the recycling of PMN integrins, and this compromises PMN migration to inflammatory sites.
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spelling doaj-art-2fec138465d04a6cb6c9c9a2fc6278c22025-02-03T01:05:01ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/27130742713074Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and MigrationJouda Gamara0Lynn Davis1Emmanuelle Rollet-Labelle2Tsunaki Hongu3Yuji Funakoshi4Yasunori Kanaho5Fawzi Aoudjit6Sylvain G. Bourgoin7Division of Infectious Disease and Immunology, CHU de Quebec Research Center, Quebec, QC, G1V 4G2, CanadaDivision of Infectious Disease and Immunology, CHU de Quebec Research Center, Quebec, QC, G1V 4G2, CanadaDivision of Infectious Disease and Immunology, CHU de Quebec Research Center, Quebec, QC, G1V 4G2, CanadaDepartment of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba 305-8575, JapanDepartment of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba 305-8575, JapanDepartment of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba 305-8575, JapanDivision of Infectious Disease and Immunology, CHU de Quebec Research Center, Quebec, QC, G1V 4G2, CanadaDivision of Infectious Disease and Immunology, CHU de Quebec Research Center, Quebec, QC, G1V 4G2, CanadaChemoattractant sensing, adhesiveness, and migration are critical events underlying the recruitment of neutrophils (PMNs) to sites of inflammation or infection. Defects in leukocyte adhesion or migration result in immunodeficiency disorders characterized by recurrent infections. In this study, we evaluated the role of Arf6 on PMN adhesion in vitro and on migration to inflammatory sites using PMN-Arf6 conditional knockout (cKO) mice. In PMN-like PLB-985 silenced for Arf6 fMLP-mediated adhesion to the β2 integrin ligands, ICAM-1 and fibrinogen or the β1/β2 integrin ligand fibronectin was significantly reduced. Furthermore, overexpression of wild-type Arf6 promoted basal and fMLP-induced adhesion to immobilized integrin ligands, while overexpression of the dominant-negative Arf6 has the opposite effects. Using the Elane-Cre deleting mouse strains, we report that the level of Arf6 deletion in inflammatory PMNs isolated from the dorsal air pouches was stronger when compared to naïve cells isolated from the bone marrow. In PMN-Arf6 cKO mice, the recruitment of PMNs into the dorsal air pouch injected with LPS or the chemoattractant fMLP was significantly diminished. Impaired cell migration correlated with reduced cell surface expression of CD11a and CD11b in Arf6 cKO PMNs. Our results highlight that Arf6 regulates the activity and possibly the recycling of PMN integrins, and this compromises PMN migration to inflammatory sites.http://dx.doi.org/10.1155/2020/2713074
spellingShingle Jouda Gamara
Lynn Davis
Emmanuelle Rollet-Labelle
Tsunaki Hongu
Yuji Funakoshi
Yasunori Kanaho
Fawzi Aoudjit
Sylvain G. Bourgoin
Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
Mediators of Inflammation
title Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
title_full Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
title_fullStr Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
title_full_unstemmed Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
title_short Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
title_sort assessment of arf6 deletion in plb 985 differentiated in neutrophil like cells and in mouse neutrophils impact on adhesion and migration
url http://dx.doi.org/10.1155/2020/2713074
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