MACROPHAGE ITGB3

Cell autonomous role of beta3 integrin: function in macrophages

Coordinatore	UNIVERSITE DU LUXEMBOURG    more  Organization address address: AVENUE DE LA FAIENCERIE 162 A city: LUXEMBOURG-VILLE postcode: 1511 contact info Titolo: Mr. Nome: Alfred Cognome: Funk Email: send email Telefono: +352 466644 6586 Fax: +352 466644 6215
Nazionalità Coordinatore	Luxembourg [LU]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-09-01   -   2017-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITE DU LUXEMBOURG  Organization address address: AVENUE DE LA FAIENCERIE 162 A city: LUXEMBOURG-VILLE postcode: 1511 contact info Titolo: Mr. Nome: Alfred Cognome: Funk Email: send email Telefono: +352 466644 6586 Fax: +352 466644 6215	LU (LUXEMBOURG-VILLE)	coordinator	100˙000.00

Mappa

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 Obiettivo del progetto (Objective)

'Integrins play a key role in the binding of cells to the extra-cellular matrix, cell migration, cell-cell adhesion and cell-cell signaling. The ß3-integrin subunit is expressed in a wide range of tissues. β3 integrins occur i.e. as αvβ3 in various cell types but as αIIβ3 exclusively in megakaryo/-thrombocytes. Mice with a germline β3 integrin deficiency (β3-/-) show enhanced tumor growth and neoangiogenesis due to angiogenic signaling in endothelial cells, and are prone to systemic inflammation and atherosclerosis on high fat diet despite a severe bleeding predisposition. Based on the complex results from germline gene targeting and antibody based loss of function experiments, a cell-autonomous role of the β3 integrin is very likely. I have demonstrated that bone marrow derived β3 integrin is strongly implicated in diet induced pneumonitis, atherosclerosis and death in hyperlipidemic β3 integrin-deficient mice vivo supporting the hypothesis that β3 integrin-dependent signaling in macrophages may be anti-inflammatory. In this proposal, I would like to study the cell-specific role of β3 integrin in macrophage populations. The susceptibility to high-fat diet induced inflammation will be investigated employing newly generated mice that allow the tissue-specific deletion of the β3 integrin combined with the possibility of following the beta3 integrin expression in macrophages in vivo on the basis of a fluorescent marker. We will utilize high-throughput technologies to identify and reconstruct molecular pathways associated with β3 integrin deficiency in macrophages with regards to inflammation and atherogenesis. We will also test whether the rescue of macrophage specific expression of β3 integrin is sufficient to correct the β3 integrin deficient phenotype. Knowledge about the cell-specific function of β3 integrin is important for clinical use of non-selective β3 integrin antagonists and may illuminate novel molecular pathways in (vascular) inflammation and cancer.'