Nicolas Raymond

Publications (4)25.52 Total impact

• Source

  Available from: Frederic Perros

  Dataset: Cytotoxic cell Granulysin PVOD PAH - Perros - AJRCCM in press

  Frédéric Perros, Sylvia Cohen-Kaminsky, Natalia Gambaryan, Barbara Girerd, Nicolas Raymond, Isabelle Klingelschmitt, Alice Huertas, Olaf Mercier, Elie Fadel, Gerald Simonneau, Marc Humbert, Peter Dorfmüller, David Montani
• Source

  Available from: Frederic Perros

  Article: Cytotoxic Cells and Granulysin in Pulmonary Arterial Hypertension and Veno-Occlusive Disease.

  Frédéric Perros, Sylvia Cohen-Kaminsky, Natalia Gambaryan, Barbara Girerd, Nicolas Raymond, Isabelle Klingelschmitt, Alice Huertas, Olaf Mercier, Elie Fadel, Gerald Simonneau, Marc Humbert, Peter Dorfmüller, David Montani
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  ABSTRACT: Rational: Pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) both display occlusive remodeling of the pulmonary vasculature responsible for increased pulmonary vascular resistances. Cytotoxic T-(CTL), Natural Killer-(NK) and Natural Killer T-(NKT) cells play a critical role in vascular remodeling in different physiological and pathological conditions. Granulysin (GNLY) represents a powerful effector protein for all these subpopulations. OBJECTIVES: To analyze the cytolytic compartment of inflammatory cells in PAH and PVOD patients. METHODS: The overall functional status of the cytolytic compartment was studied through epigenetic analysis of the GNLY gene in explanted lungs and in PBMC. Flow cytometry technology allowed analysis of specific circulating cytolytic cells and GNLY contents. A GNLY-specific ELISA allowed measurement of GNLY serum concentrations. MEASUREMENTS AND MAIN RESULTS: A decrease in GNLY demethylation in the gDNA extracted from PBMC and explanted lungs was found specifically in PVOD but not in PAH. This was associated with a decrease in populations and subpopulations of CTL and NKT, and an increase of NK populations. Despite the reduced granulysin-containing cells in PVOD patients, GNLY serum levels were higher, suggesting these cells were wasting their content. Furthermore, the increase of GNLY concentration in the serum of PVOD was significantly higher than in PAH patients. CONCLUSIONS: PVOD is characterized by alterations of circulating cytotoxic cell-subpopulations and by epigenetic dysregulation within the GNLY gene. Our findings may be helpful in the quest to develop needed diagnostic tools, including flow cytometry analyses, in order to screen for suspected PVOD in patients with pulmonary hypertension.
  American Journal of Respiratory and Critical Care Medicine 12/2012; · 11.08 Impact Factor
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  Available from: David Montani

  Article: Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension.

  Frédéric Perros, Peter Dorfmüller, David Montani, Hamida Hammad, Wim Waelput, Barbara Girerd, Nicolas Raymond, Olaf Mercier, Sacha Mussot, Sylvia Cohen-Kaminsky, Marc Humbert, Bart N Lambrecht
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  ABSTRACT: Patients with idiopathic pulmonary arterial hypertension (IPAH) present circulating autoantibodies against vascular wall components. Pathogenic antibodies may be generated in tertiary (ectopic) lymphoid tissues (tLTs). To assess the frequency of tLTs in IPAH lungs, as compared with control subjects and flow-induced PAH in patients with Eisenmenger syndrome, and to identify local mechanisms responsible for their formation, perpetuation, and function. tLT composition and structure were studied by multiple immunostainings. Cytokine/chemokine and growth factor expression was quantified by real-time polymerase chain reaction and localized by immunofluorescence. The systemic mark of pulmonary lymphoid neogenesis was investigated by flow cytometry analyses of circulating lymphocytes. As opposed to lungs from control subjects and patients with Eisenmenger syndrome, IPAH lungs contained perivascular tLTs, comprising B- and T-cell areas with high endothelial venules and dendritic cells. Lymphocyte survival factors, such as IL-7 and platelet-derived growth factor-A, were expressed in tLTs as well as the lymphorganogenic cytokines/chemokines, lymphotoxin-α/-β, CCL19, CCL20, CCL21, and CXCL13, which might explain the depletion of circulating CCR6(+) and CXCR5(+) lymphocytes. tLTs were connected with remodeled vessels via an ER-TR7(+) stromal network and supplied by lymphatic channels. The presence of germinal center centroblasts, follicular dendritic cells, activation-induced cytidine deaminase, and IL-21(+)PD1(+) follicular helper T cells in tLTs together with CD138(+) plasma cell accumulation around remodeled vessels in areas of immunoglobulin deposition argued for local immunoglobulin class switching and ongoing production. We highlight the main features of lymphoid neogenesis specifically in the lungs of patients with IPAH, providing new evidence of immunological mechanisms in this severe condition.
  American Journal of Respiratory and Critical Care Medicine 11/2011; 185(3):311-21. · 11.08 Impact Factor
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  Available from: Frederic Perros

  Article: Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension.

  Peter Dorfmüller, Marie-Camille Chaumais, Maria Giannakouli, Ingrid Durand-Gasselin, Nicolas Raymond, Elie Fadel, Olaf Mercier, Frédéric Charlotte, David Montani, Gérald Simonneau, Marc Humbert, Frédéric Perros
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  ABSTRACT: Involvement of inflammation in pulmonary hypertension (PH) has previously been demonstrated and recently, immune-modulating dendritic cells (DCs) infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH) and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS), as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT), monocrotaline-exposure/pneumonectomy (MCT/PE). Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine) in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature. Immunolabeling for OX62, CD68 and actin revealed adventitial and medial DC- and monocyte-infiltration; in MCT/PE, medial smooth muscle cells were admixed with CD68+/vimentin+ cells. Our experimental findings support a new concept of immunologic responses to increased OS in MCT/PE-induced PAH, possibly linking recruitment of dendritic cells and OS-producing mast-cells to characteristic vasculopathy.
  Respiratory research 09/2011; 12:119. · 3.36 Impact Factor