TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.

<h4>Aims</h4>We investigated the role of the TLR4-accessory molecule RP105 (CD180) in post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4-mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective neovascularization. Immunohistochemical ana...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Antonius J N M Bastiaansen, Jacco C Karper, Anouk Wezel, Hetty C de Boer, Sabine M J Welten, Rob C M de Jong, Erna A B Peters, Margreet R de Vries, Annemarie M van Oeveren-Rietdijk, Anton Jan van Zonneveld, Jaap F Hamming, A Yaël Nossent, Paul H A Quax
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/65af4eb8c5d64c42a1a40f906225c2e5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:65af4eb8c5d64c42a1a40f906225c2e5
record_format	dspace
spelling	oai:doaj.org-article:65af4eb8c5d64c42a1a40f906225c2e52021-11-18T08:15:03ZTLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.1932-620310.1371/journal.pone.0099882https://doaj.org/article/65af4eb8c5d64c42a1a40f906225c2e52014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945347/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>We investigated the role of the TLR4-accessory molecule RP105 (CD180) in post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4-mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective neovascularization. Immunohistochemical analyses revealed that RP105+ monocytes are present in the perivascular space of remodeling collateral arterioles. As RP105 inhibits TLR4 signaling, we hypothesized that RP105 deficiency would lead to an unrestrained TLR4-mediated inflammatory response and hence to enhanced blood flow recovery after ischemia.<h4>Methods and results</h4>RP105-/- and wild type (WT) mice were subjected to hind limb ischemia and blood flow recovery was followed by Laser Doppler Perfusion Imaging. Surprisingly, we found that blood flow recovery was severely impaired in RP105-/- mice. Immunohistochemistry showed that arteriogenesis was reduced in these mice compared to the WT. However, both in vivo and ex vivo analyses showed that circulatory pro-arteriogenic Ly6Chi monocytes were more readily activated in RP105-/- mice. FACS analyses showed that Ly6Chi monocytes became activated and migrated to the affected muscle tissues in WT mice following induction of hind limb ischemia. Although Ly6Chi monocytes were readily activated in RP105-/- mice, migration into the ischemic tissues was hampered and instead, Ly6Chi monocytes accumulated in their storage compartments, bone marrow and spleen, in RP105-/- mice.<h4>Conclusions</h4>RP105 deficiency results in an unrestrained inflammatory response and monocyte over-activation, most likely due to the lack of TLR4 regulation. Inappropriate, premature systemic activation of pro-inflammatory Ly6Chi monocytes results in reduced infiltration of Ly6Chi monocytes in ischemic tissues and in impaired blood flow recovery.Antonius J N M BastiaansenJacco C KarperAnouk WezelHetty C de BoerSabine M J WeltenRob C M de JongErna A B PetersMargreet R de VriesAnnemarie M van Oeveren-RietdijkAnton Jan van ZonneveldJaap F HammingA Yaël NossentPaul H A QuaxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e99882 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonius J N M Bastiaansen Jacco C Karper Anouk Wezel Hetty C de Boer Sabine M J Welten Rob C M de Jong Erna A B Peters Margreet R de Vries Annemarie M van Oeveren-Rietdijk Anton Jan van Zonneveld Jaap F Hamming A Yaël Nossent Paul H A Quax TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
description	<h4>Aims</h4>We investigated the role of the TLR4-accessory molecule RP105 (CD180) in post-ischemic neovascularization, i.e. arteriogenesis and angiogenesis. TLR4-mediated activation of pro-inflammatory Ly6Chi monocytes is crucial for effective neovascularization. Immunohistochemical analyses revealed that RP105+ monocytes are present in the perivascular space of remodeling collateral arterioles. As RP105 inhibits TLR4 signaling, we hypothesized that RP105 deficiency would lead to an unrestrained TLR4-mediated inflammatory response and hence to enhanced blood flow recovery after ischemia.<h4>Methods and results</h4>RP105-/- and wild type (WT) mice were subjected to hind limb ischemia and blood flow recovery was followed by Laser Doppler Perfusion Imaging. Surprisingly, we found that blood flow recovery was severely impaired in RP105-/- mice. Immunohistochemistry showed that arteriogenesis was reduced in these mice compared to the WT. However, both in vivo and ex vivo analyses showed that circulatory pro-arteriogenic Ly6Chi monocytes were more readily activated in RP105-/- mice. FACS analyses showed that Ly6Chi monocytes became activated and migrated to the affected muscle tissues in WT mice following induction of hind limb ischemia. Although Ly6Chi monocytes were readily activated in RP105-/- mice, migration into the ischemic tissues was hampered and instead, Ly6Chi monocytes accumulated in their storage compartments, bone marrow and spleen, in RP105-/- mice.<h4>Conclusions</h4>RP105 deficiency results in an unrestrained inflammatory response and monocyte over-activation, most likely due to the lack of TLR4 regulation. Inappropriate, premature systemic activation of pro-inflammatory Ly6Chi monocytes results in reduced infiltration of Ly6Chi monocytes in ischemic tissues and in impaired blood flow recovery.
format	article
author	Antonius J N M Bastiaansen Jacco C Karper Anouk Wezel Hetty C de Boer Sabine M J Welten Rob C M de Jong Erna A B Peters Margreet R de Vries Annemarie M van Oeveren-Rietdijk Anton Jan van Zonneveld Jaap F Hamming A Yaël Nossent Paul H A Quax
author_facet	Antonius J N M Bastiaansen Jacco C Karper Anouk Wezel Hetty C de Boer Sabine M J Welten Rob C M de Jong Erna A B Peters Margreet R de Vries Annemarie M van Oeveren-Rietdijk Anton Jan van Zonneveld Jaap F Hamming A Yaël Nossent Paul H A Quax
author_sort	Antonius J N M Bastiaansen
title	TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
title_short	TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
title_full	TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
title_fullStr	TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
title_full_unstemmed	TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
title_sort	tlr4 accessory molecule rp105 (cd180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/65af4eb8c5d64c42a1a40f906225c2e5
work_keys_str_mv	AT antoniusjnmbastiaansen tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT jaccockarper tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT anoukwezel tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT hettycdeboer tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT sabinemjwelten tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT robcmdejong tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT ernaabpeters tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT margreetrdevries tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT annemariemvanoeverenrietdijk tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT antonjanvanzonneveld tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT jaapfhamming tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT ayaelnossent tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel AT paulhaquax tlr4accessorymoleculerp105cd180regulatesmonocytedrivenarteriogenesisinamurinehindlimbischemiamodel
_version_	1718421988019535872

TLR4 accessory molecule RP105 (CD180) regulates monocyte-driven arteriogenesis in a murine hind limb ischemia model.

Ejemplares similares