avances en el desarrollo de terapias neutralizantes en la sepsis advances in the development of neutralizing therapies for sepsis

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ID: 146148
2006
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Abstract
El lipopolisacárido bacteriano (LPS), también denominado endotoxina, es el constituyente mayoritario de la membrana externa de bacterias Gram negativas. Esta molécula es liberada de la bacteria a la circulación exhibiendo una amplia variedad de efectos tóxicos y pro-inflamatorios, los cuales están asociados al lípido A y a su vez están relacionados a la patogénesis de la sepsis. Muchos de los fenómenos fisiológicos producidos por el LPS resultan de la capacidad de esta molécula de activar las células del sistema inmune del huésped, entre ellas monocitos, macrófagos y leucocitos polimorfonucleares. Este proceso produce una inflamación local, proceso beneficioso para el huésped. Sin embargo, si la cantidad de LPS liberado excede cierta concentración crítica umbral, la exacerbada liberación de citoquinas inflamatorias como Factor de Necrosis Tumoral (TNF-a) e interleuquinas (IL) resulta en sepsis grave, lo que hace necesario encontrar nuevas opciones terapéuticas capaces de neutralizar la endotoxina circulante. En este artículo se presenta una revisión actualizada de los resultados experimentales obtenidos in vivo e in vitro empleando proteínas y péptidos sintéticos con la finalidad de neutralizar el LPS, y las perspectivas que en este área ofrece el uso de lipoproteínas, en particular la apolipoproteína A-I y formas mutantes o péptidos derivados de esta proteína.
Lipopolisaccharide (LPS), also called endotoxin, is the major component of the external membrane in Gram negative bacteria. This molecule is released to circulation by the bacteria, producing a large variety of toxic and pro-inflammatory effects which are associated with lipid A as well as with sepsis pathogenesis. Many physiological phenomena produced by LPS arise from this molecule's capacity to activate cells in the host immune system such as monocytes, macrophages and polymorphonuclear leukocytes. This process leads to a local inflammation, and it is beneficial for the host. However, if the amount of LPS released exceeds the critical concentration threshold an augmented release of inflammatory cytokines as TNF-a, and interleukines (IL) produce a severe sepsis. This fact led us to find therapeutical alternatives able to neutralize circulating endotoxin. This work is focused on the experimental results obtained in vivo and in vitro using synthetic proteins and peptides in order to neutralize LPS, and on future perpectives in this research area that offer the use of lipoprotein and in particular apolipoprotein A-I and mutants or peptides derived from this protein.
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Authors ;Maria Florencia Henning;Horacio Garda;Laura Bakás
Journal proceedings on: 2016 ieee central america and panama student conference, conescapan 2016
Year 2006
DOI
DOI not found
URL
http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802006000300014
Keywords
endotoxin lipopolysaccharide sepsis hdl allergyinfectious and parasitic diseases apolipoprotein a-imedicineimmunologic diseases

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