RESUMO
El lipopolisacarido bacteriano (LPS), tambien denominado endotoxina, es el constituyente mayoritario de la membrana externa de bacterias Gram negativas. Esta molecula es liberada de la bacteria a la circulacion exhibiendo una amplia variedad de efectos toxicos y pro-inflamatorios, los cuales estan asociados al lipido A y a su vez estan relacionados a la patogenesis de la sepsis. Muchos de los fenomenos fisiologicos producidos por el LPS resultan de la capacidad de esta molecula de activar las celulas del sistema inmune del huesped, entre ellas monocitos, macrofagos y leucocitos polimorfonucleares. Este proceso produce una inflamacion local, proceso beneficioso para el huesped. Sin embargo, si la cantidad de LPS liberado excede cierta concentracion critica umbral, la exacerbada liberacion de citoquinas inflamatorias como Factor de Necrosis Tumoral (TNF-alfa) e interleuquinas (IL) resulta en sepsis grave, lo que hace necesario encontrar nuevas opciones terapeuticas capaces de neutralizar la endotoxina circulante. En este articulo se presenta una revision actualizada de los resultados experimentales obtenidos in vivo e in vitro empleando proteinas y peptidos sinteticos con la finalidad de neutralizar el LPS, y las perspectivas que en este area ofrece el uso de lipoproteinas, en particular la apolipoproteina A-I y formas mutantes o peptidos derivados de esta proteina.
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 henomena 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 thresholdan augmented release of inflammatory cytokines as TNF-alfa, 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 neutralizeLPS, 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.