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Artículo

Novel use of all-trans-retinoic acid in a model of lipopolysaccharide-immunosuppression to decrease the generation of myeloid-derived suppressor cells by reducing the proliferation of cd34+ precursor cells

Martire Greco, DaianaIcon ; Rodriguez Rodrigues, Nahuel EmilianoIcon ; Castillo Montañez, Luis AlejandroIcon ; Vecchione, María BelénIcon ; de Campos Nebel, Ildefonso MarceloIcon ; Córdoba Moreno, Marlina OlyissaIcon ; Meiss, Roberto; Vermeulen, Elba MonicaIcon ; Landoni, Verónica InésIcon ; Fernández, Gabriela CristinaIcon
Fecha de publicación: 01/07/2017
Editorial: Lippincott Williams
Revista: Shock
ISSN: 1073-2322
e-ISSN: 1540-0514
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

All-trans-Retinoic Acid (ATRA) is a derivative of vitamin A with anti-proliferative properties. Endotoxin shock and subsequent immunosuppression (IS) by lipopolysaccharide (LPS) stimulates myelopoiesis with expansion of myeloid-derived suppressor cells (MDSC). Since we have previously shown that ATRA reverses the IS state by decreasing functional MDSC, our aim was to investigate if ATRA was able to modulate MDSC generation by regulating myelopoiesis in murine hematopoietic organs. We found that ATRA administration in vivo and in vitro decreased the number of CD34+ precursor cells that were increased in IS mice. When we studied the cellular mechanisms involved, we did not find any differences in apoptosis of CD34+ precursors or in the differentiation of these cells to their mature counterparts. Surprisingly, ATRA decreased precursor proliferation, in vitro and in vivo, as assessed by a reduction in the size and number of colony forming units (CFU) generated from CD34+ cells and by a decreased incorporation of H-thymidine. Moreover, ATRA administration to IS mice decreased the number of MDSC in the spleen, with a restoration of T lymphocyte proliferation and a restitution of the histological architecture. Our results indicate, for the first time, a new use of ATRA to abolish LPS-induced myelopoiesis, affecting the proliferation of precursor cells, and in consequence, decreasing MDSC generation, having a direct impact on the improvement of immune competence. Administration of ATRA could overcome the immunosuppressive state generated by sepsis that often leads to opportunistic life-threatening infections. Therefore, ATRA could be considered a complementary treatment to enhance immune responses
Palabras clave: Retinoic Acid , Lps , Myeliod Supressor Cells , Colonic Former Units
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/45020
URL: https://journals.lww.com/shockjournal/Abstract/2017/07000/Novel_Use_of_All_Trans
DOI: http://dx.doi.org/ 10.1097/SHK.0000000000000812
Colecciones
Articulos(IMEX)
Articulos de INST.DE MEDICINA EXPERIMENTAL
Citación
Martire Greco, Daiana; Rodriguez Rodrigues, Nahuel Emiliano; Castillo Montañez, Luis Alejandro; Vecchione, María Belén; de Campos Nebel, Ildefonso Marcelo; et al.; Novel use of all-trans-retinoic acid in a model of lipopolysaccharide-immunosuppression to decrease the generation of myeloid-derived suppressor cells by reducing the proliferation of cd34+ precursor cells; Lippincott Williams; Shock; 48; 1; 1-7-2017; 94-103
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