Fractalkine Expression Induces Endothelial Progenitor Cell Lysis by Natural Killer Cells

BACKGROUND: Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+)-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+) progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+) cells expressing FKN was identified as an independent variable inversely correlated to CD34(+) progenitor cell count. We further showed that treatment of CD34(+) circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+) progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients

Les moyens techniques de l’art. 2. Max Weber à l’épreuve d’un siècle d’histoire musicale

cote interne IRCAM: Despoix08cNone / NoneNational audienceLes moyens techniques de l’art. 2. Max Weber à l’épreuve d’un siècle d’histoire musical

Les moyens techniques de l’art. 1. Portée de la sociologie musicale de Max Weber

cote interne IRCAM: Despoix08bNone / NoneNational audienceLes moyens techniques de l’art. 1. Portée de la sociologie musicale de Max Webe

Synchronisations, désynchronisations. Le jeu intermédial des corps, des écritures et des instruments

Cet article introduit au dossier « synchroniser / synchronizing » qui propose aussi bien d’esquisser une archéologie des modes de (dé)synchronisation qu’interroger leur multiplicité actuelle à la croisée des arts des images et de ceux du son et de la musique.This article introduces the “synchroniser / synchronizing” issue of Intermédialités / Intermediality by tracing an archeology of various types of (de)synchronizations at the crossroads between the realms of images, sound and music

Contribution à l'étude des fonctions de la molécule d'hadérence endothéliale CD146

Mon travail de thèse représente une contribution à l étude des fonctions de CD146, puisque j ai développé des souris CD146 knock-out, identifié un ligand pour CD146 et montré une différence d expression leucocytaire de CD146 entre l homme et la souris. Les souris CD146 KO sont viables et fertiles. Le phénotype de ces souris pour l implication de CD146 dans le développement vasculaire et la transmigration leucocytaire ou tumorale est en cours d évaluation. A la recherche d un ligand de la mucine CD146/Muc18, j ai pu montré que la galectine 1 était capable d interagir directement avec la partie extracellulaire de CD146. Cette interaction est dépendante des sucres et affiche un KD de 3.10-7 M. Cette association n est retrouvée in vivo que lors de condition pro-inflammatoire et sur des cellules endothéliales non confluentes. Elle semble impliquée dans la survie des cellules endothéliales. Bien que n étant pas exprimée sur les cellules NK humaines, la production de nouveaux anticorps monoclonaux a permis de montrer que CD146 l est sur celles d origine murine. Plus qu un marqueur spécifique de ces cellules au sein des lymphocytes, le niveau d expression de CD146 détermine la maturité de ces cellules.Increasing knowledge of CD146 functions has been the aim of my PhD. To address this issue, a CD146 knock-out mice was generated, one ligand was identified and a new differential expression of CD146 on leukocyte between human and mice was demonstrated. KO mice are viable and fertile. Involvement of CD146 during the vascular development, the leukocyte transmigration and metastatic ability of tumor cells are actually in process. Looking for a ligand of the mucin CD146/ MUC18, I showed that galectin-1 is able to interact directly with the extracellular part of CD146. This interaction is dependant of CD146 s sugar ramifications and the KD is 3.10-7 M. In vivo, this interaction only occurs in inflammatory conditions on non-confluent endothelial cells and seems to be implicated in endothelial cell survival. Conversely to human NK cells, the generation of a new set of monoclonal anibody allowed us to prove that mouse NK cells do express CD146. Indeed this expression increases during NK cell maturation and is restricted to NK cells among mouse lymphocytes.AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Relire un essai weberien méconnu : motifs et obstacles

cote interne IRCAM: Despoix08aNone / NoneNational audienceRelire un essai weberien méconnu : motifs et obstacle

Synchroniser/Synchronize

cote interne IRCAM: Despoix12bNone / NoneNational audienceSynchroniser/Synchroniz

Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

Breast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca2+ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP3R) is a major player in the regulation of the Ca2+ flux from the endoplasmic reticulum to the cytoplasm. The IP3Rs (and particularly the IP3R3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IP3Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP3R3 and IP3R1 (but not IP3R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP3R3 subtype was expressed more strongly than the IP3R1 and IP3R2 subtypes. Furthermore, the expression of IP3R3 (but not of IP3R1 or IP3R2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IP3Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP3R subtypes, IP3R3 expression is upregulated in breast cancer and is correlated with prognostic factors