TY - JOUR
T1 - Invasive amebiasis
T2 - A microcirculatory disorder?
AU - Campos-Rodríguez, Rafael
AU - Jarillo-Luna, Rosa Adriana
AU - Larsen, Bruce Allan
AU - Rivera-Aguilar, Víctor
AU - Ventura-Juárez, Javier
N1 - Funding Information:
This work was supported by SIP, COFAA and CONACYT (grant 49749).
PY - 2009/11
Y1 - 2009/11
N2 - The two current models of invasive amebiasis both hold that direct contact of toxic molecules and amebas with tissue produces the necrotic areas characteristic of this disorder. Whereas one model characterizes these toxic molecules as amebic products (e.g., lectins, amebapores, cysteine proteinases and other proteolytic enzymes), the other describes them as products of the inflammatory response (e.g., cytokines, nitric oxide, reactive oxygen intermediates and cytotoxic granules). Both these models can account for necrotic areas with many amebas present and with acute inflammation, but not those with few or no amebas present or with scarce inflammation. A new model poses that an inadequate immune response leads to a continuous and prolonged activation of endothelial cells (ECs) by amebas, amebic molecules and cytokines, which triggers the mechanisms leading to necrosis. Other toxic molecules later contribute to EC activation: nitric oxide, reactive oxygen intermediates, the activated complement and proteases. Hyperactivated endothelial cells continuously express adhesion molecules (e.g., ICAM-1 and E-selectin), pro-coagulant molecules (e.g., tissue factor, von Willebrand factor, and the plasminogen activator inhibitor), resulting in ever greater inflammation and thrombosis, which eventually reduces or blocks blood flow in some vessels and starves certain tissue areas of an adequate oxygen and nutrient supply. When necrotic areas first develop, they are surrounded by inflammatory cells due to the acute inflammation at this stage. However, these cells are starved of oxygen and essential nutrients by the same microcirculatory dysfunction. The increasing concentration of nitric oxide during amebiasis eventually has an anti-inflammatory and vasodilating effect, creating a new mechanism for the microcirculatory dysfunction. This local microcirculatory dysfunction can explain necrotic areas in the presence of many, few, or no amebas, with abundant or scarce inflammation.
AB - The two current models of invasive amebiasis both hold that direct contact of toxic molecules and amebas with tissue produces the necrotic areas characteristic of this disorder. Whereas one model characterizes these toxic molecules as amebic products (e.g., lectins, amebapores, cysteine proteinases and other proteolytic enzymes), the other describes them as products of the inflammatory response (e.g., cytokines, nitric oxide, reactive oxygen intermediates and cytotoxic granules). Both these models can account for necrotic areas with many amebas present and with acute inflammation, but not those with few or no amebas present or with scarce inflammation. A new model poses that an inadequate immune response leads to a continuous and prolonged activation of endothelial cells (ECs) by amebas, amebic molecules and cytokines, which triggers the mechanisms leading to necrosis. Other toxic molecules later contribute to EC activation: nitric oxide, reactive oxygen intermediates, the activated complement and proteases. Hyperactivated endothelial cells continuously express adhesion molecules (e.g., ICAM-1 and E-selectin), pro-coagulant molecules (e.g., tissue factor, von Willebrand factor, and the plasminogen activator inhibitor), resulting in ever greater inflammation and thrombosis, which eventually reduces or blocks blood flow in some vessels and starves certain tissue areas of an adequate oxygen and nutrient supply. When necrotic areas first develop, they are surrounded by inflammatory cells due to the acute inflammation at this stage. However, these cells are starved of oxygen and essential nutrients by the same microcirculatory dysfunction. The increasing concentration of nitric oxide during amebiasis eventually has an anti-inflammatory and vasodilating effect, creating a new mechanism for the microcirculatory dysfunction. This local microcirculatory dysfunction can explain necrotic areas in the presence of many, few, or no amebas, with abundant or scarce inflammation.
UR - http://www.scopus.com/inward/record.url?scp=70349841141&partnerID=8YFLogxK
U2 - 10.1016/j.mehy.2009.05.014
DO - 10.1016/j.mehy.2009.05.014
M3 - Artículo
C2 - 19540678
SN - 0306-9877
VL - 73
SP - 687
EP - 697
JO - Medical Hypotheses
JF - Medical Hypotheses
IS - 5
ER -