MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells.
Animals
Cells, Cultured
Disease Models, Animal
Disease Susceptibility
Endoglin
/ genetics
Endothelial Cells
/ metabolism
Gene Expression
Granulocyte-Macrophage Colony-Stimulating Factor
/ metabolism
Humans
Inflammation
/ etiology
Inflammation Mediators
/ metabolism
Macrophage Colony-Stimulating Factor
/ metabolism
Macrophages
/ immunology
Matrix Metalloproteinase 12
/ metabolism
Mice
Models, Biological
MMP-12
endoglin
endothelial cells
inflammation
macrophages
monocytes
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
25 Jun 2019
25 Jun 2019
Historique:
received:
30
04
2019
revised:
07
06
2019
accepted:
18
06
2019
entrez:
28
6
2019
pubmed:
28
6
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.
Identifiants
pubmed: 31242676
pii: ijms20123107
doi: 10.3390/ijms20123107
pmc: PMC6627183
pii:
doi:
Substances chimiques
Endoglin
0
Inflammation Mediators
0
Macrophage Colony-Stimulating Factor
81627-83-0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Matrix Metalloproteinase 12
EC 3.4.24.65
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministerio de Ciencia e Innovación
ID : SAF2013-43421-R to CB; SAF2017-83785-R and SAF2014-23801 to ALC
Organisme : Consejo Superior de Investigaciones Científicas
ID : 201920E022 to CB
Organisme : Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
ID : ISCIII-CB06/07/0038 to CB
Organisme : Czech Republic Specific University Research
ID : SVV-260414 to PN
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