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Mexico City, Mexico

Tamoutounour S.,Aix - Marseille University | Tamoutounour S.,French Institute of Health and Medical Research | Tamoutounour S.,French National Center for Scientific Research | Henri S.,Aix - Marseille University | And 28 more authors.
European Journal of Immunology | Year: 2012

Dendritic cells (DCs) and monocyte-derived macrophages (MΦs) are key components of intestinal immunity. However, the lack of surface markers differentiating MΦs from DCs has hampered understanding of their respective functions. Here, we demonstrate that, using CD64 expression, MΦs can be distinguished from DCs in the intestine of both mice and humans. On that basis, we revisit the phenotype of intestinal DCs in the absence of contaminating MΦs and we delineate a developmental pathway in the healthy intestine that leads from newly extravasated Ly-6Chi monocytes to intestinal MΦs. We determine how inflammation impacts this pathway and show that T cell-mediated colitis is associated with massive recruitment of monocytes to the intestine and the mesenteric lymph node (MLN). There, these monocytes differentiate into inflammatory MΦs endowed with phagocytic activity and the ability to produce inducible nitric oxide synthase. In the MLNs, inflammatory MΦs are located in the T-cell zone and trigger the induction of proinflammatory T cells. Finally, T cell-mediated colitis develops irrespective of intestinal DC migration, an unexpected finding supporting an important role for MLN-resident inflammatory MΦs in the etiology of T cell-mediated colitis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Murillo M.M.,Cancer Research UK Research Institute | Murillo M.M.,Institute of Cancer Research | Zelenay S.,Immunobiology Laboratory | Nye E.,Experimental Histopathology Laboratory | And 5 more authors.
Journal of Clinical Investigation | Year: 2014

Direct interaction of RAS with the PI3K p110α subunit mediates RAS-driven tumor development: however, it is not clear how p110α/RAS- dependant signaling mediates interactions between tumors and host tissues. Here, using a murine tumor cell transfer model, we demonstrated that disruption of the interaction between RAS and p110α within host tissue reduced tumor growth and tumor-induced angiogenesis, leading to improved survival of tumor-bearing mice, even when this interaction was intact in the transferred tumor. Furthermore, functional interaction of RAS with p110α in host tissue was required for efficient establishment and growth of metastatic tumors. Inhibition of RAS and p110α interaction prevented proper VEGF-A and FGF-2 signaling, which are required for efficient angiogenesis. Additionally, disruption of the RAS and p110α interaction altered the nature of tumor-associated macrophages, inducing expression of markers typical for macrophage populations with reduced tumor-promoting capacity. Together, these results indicate that a functional RAS interaction with PI3K p110α in host tissue is required for the establishment of a growth-permissive environment for the tumor, particularly for tumor-induced angiogenesis. Targeting the interaction of RAS with PI3K has the potential to impair tumor formation by altering the tumorhost relationship, in addition to previously described tumor cell-autonomous effects.

Barete S.,University Pierre and Marie Curie | Mouawad R.,Pitie Salpetriere Hospital | Choquet S.,Pitie Salpetriere Hospital | Viala K.,Federation of Clinical Neurophysiology | And 5 more authors.
Archives of Dermatology | Year: 2010

To investigate skin manifestations of the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and their correlation with serum vascular endothelial growth factor (s-VEGF-A) levels and to describe the impact of autologous peripheral blood stem cell transplantation (aPBSCT) on these manifestations and the correlation with s-VEGF-A levels. Design: Case series from January 1993 through June 2007. Setting: Hospitalized care in Assistance Publique-Hôpitaux de Paris in Pitié-Salpêtrière and Tenon hospitals. Patients: Twenty-three patients with POEMS syndrome, 10 of whom were clinically followed up after aPBSCT. Main Outcome Measures: Description and distribution of clinical lesions at POEMS syndrome diagnosis, skin evaluation after aPBSCT, and s-VEGF-A levels measured at POEMS syndrome diagnosis and after aPBSCT. Results: In 21 patients with skin manifestations at POEMS syndrome diagnosis, the most common skin manifestations were hemangiomas (18 patients [86%]), hyperpigmentation (16 [76%]), skin thickening (12 [57%]), acrocyanosis (12 [57%]), hypertrichosis (11 [52%]), acquired facial lipoatrophy (11 [52%]), and white nails (8 [38%]). The median s-VEGF-A level was not different between patients with and without skin manifestations except in those with hypertrichosis (P=.04). After aPBSCT, no significant correlation was observed between s-VEGF-A level decreases and response of skin manifestations, again except for hypertrichosis (P=.007). Conclusions: Acquired facial lipoatrophy and livedo should be added to the skin manifestations of POEMS syndrome. Despite a role of s-VEGF-A in various skin manifestations, the impact of s-VEGF-A level decreases on skin outcomes is weak after aPBSCT, mostly resulting in clinical stabilization. ©2010 American Medical Association. All rights reserved.

Ghosh K.,Immunobiology Laboratory | Ghosh S.,Bangur Institute of Neurosciences | Chatterjee U.,SSKM Hospital | Ghosh A.,Immunobiology Laboratory
Asian Pacific Journal of Cancer Prevention | Year: 2016

Human glioma, arising from glial cells of the central nervous system, accounts for almost 30%of all brain tumours , neoplasms with a poor prognosis and high mortality rates worldwide. In the present study we assessed tissue architectural modifications associated with macrophage lineage cells, controversial major immune effector cells within the brain, in human glioma tissue samples from eastern India. Ethically cleared post-operative human glioma samples from our collaborative neurosurgery unit with respective CT/MRI and patient history were collected from the Nodal Centre of Neurosciences in Kolkata, over 9 months. Along with conventional histopathology, samples were subjected to silver-gold staining and fluorescence tagged immunophenotyping for the detection of electron dense brain macrophage/microglia cells in glioma tissue, followed by immune-phenotyping of cells. With higher grades, CD11b+/Iba-1+ macrophage/microglia architecture with de-structured boundaries of glioma lesions indicated malfunction and invasive effector state. Present study documented a contribution of microglia to glioma progression in Eastern India.

Moreno-Eutimio M.A.,Immunobiology Laboratory | Nieto-Velazquez N.G.,Immunobiology Laboratory | Espinosa-Monroy L.,Immunobiology Laboratory | Torres-Ramos Y.,National Institute of Perinatology | And 4 more authors.
BioMed Research International | Year: 2014

Pebisut is a biological adhesive composed of naturally occurring carbohydrates combined with zinc oxide (ZnO) initially used as a coadjutant for healing of anastomoses. Likewise some works demonstrated that carbohydrate complexes exerts anti-inflammatory activity and it is widely known that ZnO modulate inflammation. However, the direct effects of Pebisut on isolated cells and acute inflammatory responses remained to be investigated. The present study evaluated anti-inflammatory effect of Pebisut using lipopolysaccharide (LPS) stimulated human mononuclear cells, chemotaxis, and cell infiltration in vivo in a murine model of peritonitis. Our data show that human cells treated with different dilutions of Pebisut release less IL-6, IL-1β, and IL-8 after LPS stimuli compared with the control treated cells. In addition, Pebisut lacked chemotactic activity in human mononuclear cells but was able to reduce chemotaxis towards CCL2, CCL5, and CXCL12 that are representative mononuclear cells chemoattractants. Finally, in a murine model of peritonitis, we found less number of macrophages (F4/80+) and T lymphocytes (CD3+) in peritoneal lavages from animals treated with Pebisut. Our results suggest that Pebisut has anti-inflammatory activity, which might have a beneficial effect during anastomoses healing or wounds associated with excessive inflammation. © 2014 Mario Adan Moreno-Eutimio et al.

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