Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)

Autores
Wolf, Dennis; Bukosza, Nora; Engel, David; Poggi, Marjorie; Jehle, Felix; Anto Michel, Nathaly; Chen, Yung Chih; Colberg, Christian; Hoppe, Natalie; Dufner, Bianca; Boon, Louis; Blankenbach, Hermann; Hilgendorf, Ingo; von zur Muhlen, Constantin; Reinöhl, Jochen; Sommer, Björn; Marchini, Timoteo Oscar; Febbraio, Mark; Weber, Christian; Bode, Christoph; Karlheinz, Peter; Lutgens, Esther; Zirlik, Andreas
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1’s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.
Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania
Fil: Bukosza, Nora. Albert Ludwigs University of Freiburg; Alemania
Fil: Engel, David. No especifíca;
Fil: Poggi, Marjorie. No especifíca;
Fil: Jehle, Felix. Albert Ludwigs University of Freiburg; Alemania
Fil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; Alemania
Fil: Chen, Yung Chih. Baker Idi Heart And Diabetes Institute; Australia
Fil: Colberg, Christian. Albert Ludwigs University of Freiburg; Alemania
Fil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; Alemania
Fil: Dufner, Bianca. Albert Ludwigs University of Freiburg; Alemania
Fil: Boon, Louis. Cardiovascular Research Institute Maastricht; Países Bajos
Fil: Blankenbach, Hermann. Albert Ludwigs University of Freiburg; Alemania
Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania
Fil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; Alemania
Fil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; Alemania
Fil: Sommer, Björn. Ludwig Maximilians Universitat; Alemania
Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Febbraio, Mark. Baker Idi Heart And Diabetes Institute; Australia
Fil: Weber, Christian. Ludwig Maximilians Universitat; Alemania
Fil: Bode, Christoph. Albert Ludwigs University of Freiburg; Alemania
Fil: Karlheinz, Peter. Baker Idi Heart And Diabetes Institute; Australia
Fil: Lutgens, Esther. Ludwig Maximilians Universitat; Alemania
Fil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; Alemania
Materia
ADHESION MOLECULES
INFLAMMATION
MACROPHAGE
METABOLIC DISORDERS
OBESITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/151540
Acceder
id CONICETDig_5809ba6144870ae9d6323f8b746c449d
oai_identifier_str oai:ri.conicet.gov.ar:11336/151540
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)Wolf, DennisBukosza, NoraEngel, DavidPoggi, MarjorieJehle, FelixAnto Michel, NathalyChen, Yung ChihColberg, ChristianHoppe, NatalieDufner, BiancaBoon, LouisBlankenbach, HermannHilgendorf, Ingovon zur Muhlen, ConstantinReinöhl, JochenSommer, BjörnMarchini, Timoteo OscarFebbraio, MarkWeber, ChristianBode, ChristophKarlheinz, PeterLutgens, EstherZirlik, AndreasADHESION MOLECULESINFLAMMATIONMACROPHAGEMETABOLIC DISORDERSOBESITYhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1’s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; AlemaniaFil: Bukosza, Nora. Albert Ludwigs University of Freiburg; AlemaniaFil: Engel, David. No especifíca;Fil: Poggi, Marjorie. No especifíca;Fil: Jehle, Felix. Albert Ludwigs University of Freiburg; AlemaniaFil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; AlemaniaFil: Chen, Yung Chih. Baker Idi Heart And Diabetes Institute; AustraliaFil: Colberg, Christian. Albert Ludwigs University of Freiburg; AlemaniaFil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; AlemaniaFil: Dufner, Bianca. Albert Ludwigs University of Freiburg; AlemaniaFil: Boon, Louis. Cardiovascular Research Institute Maastricht; Países BajosFil: Blankenbach, Hermann. Albert Ludwigs University of Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; AlemaniaFil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; AlemaniaFil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; AlemaniaFil: Sommer, Björn. Ludwig Maximilians Universitat; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Febbraio, Mark. Baker Idi Heart And Diabetes Institute; AustraliaFil: Weber, Christian. Ludwig Maximilians Universitat; AlemaniaFil: Bode, Christoph. Albert Ludwigs University of Freiburg; AlemaniaFil: Karlheinz, Peter. Baker Idi Heart And Diabetes Institute; AustraliaFil: Lutgens, Esther. Ludwig Maximilians Universitat; AlemaniaFil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; AlemaniaSchattauer Gmbh-Verlag Medizin Naturwissenschaften2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/151540Wolf, Dennis; Bukosza, Nora; Engel, David; Poggi, Marjorie; Jehle, Felix; et al.; Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO); Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 117; 2; 1-2017; 325-3380340-6245CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1160/TH16-07-0553info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:32Zoai:ri.conicet.gov.ar:11336/151540instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:33.032CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
title Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
spellingShingle Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
Wolf, Dennis
ADHESION MOLECULES
INFLAMMATION
MACROPHAGE
METABOLIC DISORDERS
OBESITY
title_short Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
title_full Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
title_fullStr Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
title_full_unstemmed Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
title_sort Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO)
dc.creator.none.fl_str_mv Wolf, Dennis
Bukosza, Nora
Engel, David
Poggi, Marjorie
Jehle, Felix
Anto Michel, Nathaly
Chen, Yung Chih
Colberg, Christian
Hoppe, Natalie
Dufner, Bianca
Boon, Louis
Blankenbach, Hermann
Hilgendorf, Ingo
von zur Muhlen, Constantin
Reinöhl, Jochen
Sommer, Björn
Marchini, Timoteo Oscar
Febbraio, Mark
Weber, Christian
Bode, Christoph
Karlheinz, Peter
Lutgens, Esther
Zirlik, Andreas
author Wolf, Dennis
author_facet Wolf, Dennis
Bukosza, Nora
Engel, David
Poggi, Marjorie
Jehle, Felix
Anto Michel, Nathaly
Chen, Yung Chih
Colberg, Christian
Hoppe, Natalie
Dufner, Bianca
Boon, Louis
Blankenbach, Hermann
Hilgendorf, Ingo
von zur Muhlen, Constantin
Reinöhl, Jochen
Sommer, Björn
Marchini, Timoteo Oscar
Febbraio, Mark
Weber, Christian
Bode, Christoph
Karlheinz, Peter
Lutgens, Esther
Zirlik, Andreas
author_role author
author2 Bukosza, Nora
Engel, David
Poggi, Marjorie
Jehle, Felix
Anto Michel, Nathaly
Chen, Yung Chih
Colberg, Christian
Hoppe, Natalie
Dufner, Bianca
Boon, Louis
Blankenbach, Hermann
Hilgendorf, Ingo
von zur Muhlen, Constantin
Reinöhl, Jochen
Sommer, Björn
Marchini, Timoteo Oscar
Febbraio, Mark
Weber, Christian
Bode, Christoph
Karlheinz, Peter
Lutgens, Esther
Zirlik, Andreas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADHESION MOLECULES
INFLAMMATION
MACROPHAGE
METABOLIC DISORDERS
OBESITY
topic ADHESION MOLECULES
INFLAMMATION
MACROPHAGE
METABOLIC DISORDERS
OBESITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1’s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.
Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania
Fil: Bukosza, Nora. Albert Ludwigs University of Freiburg; Alemania
Fil: Engel, David. No especifíca;
Fil: Poggi, Marjorie. No especifíca;
Fil: Jehle, Felix. Albert Ludwigs University of Freiburg; Alemania
Fil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; Alemania
Fil: Chen, Yung Chih. Baker Idi Heart And Diabetes Institute; Australia
Fil: Colberg, Christian. Albert Ludwigs University of Freiburg; Alemania
Fil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; Alemania
Fil: Dufner, Bianca. Albert Ludwigs University of Freiburg; Alemania
Fil: Boon, Louis. Cardiovascular Research Institute Maastricht; Países Bajos
Fil: Blankenbach, Hermann. Albert Ludwigs University of Freiburg; Alemania
Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania
Fil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; Alemania
Fil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; Alemania
Fil: Sommer, Björn. Ludwig Maximilians Universitat; Alemania
Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Febbraio, Mark. Baker Idi Heart And Diabetes Institute; Australia
Fil: Weber, Christian. Ludwig Maximilians Universitat; Alemania
Fil: Bode, Christoph. Albert Ludwigs University of Freiburg; Alemania
Fil: Karlheinz, Peter. Baker Idi Heart And Diabetes Institute; Australia
Fil: Lutgens, Esther. Ludwig Maximilians Universitat; Alemania
Fil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; Alemania
description Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1’s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/151540
Wolf, Dennis; Bukosza, Nora; Engel, David; Poggi, Marjorie; Jehle, Felix; et al.; Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO); Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 117; 2; 1-2017; 325-338
0340-6245
CONICET Digital
CONICET
url http://hdl.handle.net/11336/151540
identifier_str_mv Wolf, Dennis; Bukosza, Nora; Engel, David; Poggi, Marjorie; Jehle, Felix; et al.; Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11B/CD18) in diet-induced obesity (DIO); Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 117; 2; 1-2017; 325-338
0340-6245
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1160/TH16-07-0553
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Schattauer Gmbh-Verlag Medizin Naturwissenschaften
publisher.none.fl_str_mv Schattauer Gmbh-Verlag Medizin Naturwissenschaften
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268673849425920
score 13.13397

Publicaciones similares