OBJECTIVE: This study investigated the role of 5-lipoxygenase in the pathogenesis of multiple organ failure (MOF) induced by zymosan. DESIGN: Male mice with a targeted disruption of the 5-lipoxygenase gene (5-LOKO) and littermate wild-type (WT) controls (5-LOWT) were used to evaluate the role of 5-lipoxygenase (5-LO) in the pathogenesis of MOF. SETTING: University research laboratory. INTERVENTIONS AND MEASUREMENTS: MOF was induced by peritoneal injection of zymosan (500 mg/kg i.p. as a suspension in saline) in 5-LOWT and in 5-LOKO mice. MOF was assessed 18 h after administration of zymosan and monitored for 12 days (for loss of body weight and mortality). RESULTS: A severe inflammatory process induced by zymosan administration in WT mice coincided with the damage of lung and small intestine, as assessed by histological examination. Myeloperoxidase activity indicative of neutrophil infiltration and lipid peroxidation were significantly increased in zymosan-treated WT mice. Zymosan in the WT mice also induced a significant increase in the plasma level of nitrite/nitrate. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to ICAM-1 and P-selectin in the lung and intestine of zymosan-treated WT mice. In contrast, the degree of (a) peritoneal inflammation and tissue injury, (b) upregulation/expression of P-selectin and ICAM-1, and (c) neutrophil infiltration were markedly reduced in intestine and lung tissue obtained from zymosan-treated 5-LO deficient mice. Zymosan-treated 5-LOKO showed also a significantly decreased mortality. CONCLUSIONS: These findings clearly demonstrate that 5-LO exerts a role in zymosan-induced nonseptic shock.
OBJECTIVE: This study investigated the role of 5-lipoxygenase in the pathogenesis of multiple organ failure (MOF) induced by zymosan. DESIGN: Male mice with a targeted disruption of the 5-lipoxygenase gene (5-LOKO) and littermate wild-type (WT) controls (5-LOWT) were used to evaluate the role of 5-lipoxygenase (5-LO) in the pathogenesis of MOF. SETTING: University research laboratory. INTERVENTIONS AND MEASUREMENTS: MOF was induced by peritoneal injection of zymosan (500 mg/kg i.p. as a suspension in saline) in 5-LOWT and in 5-LOKO mice. MOF was assessed 18 h after administration of zymosan and monitored for 12 days (for loss of body weight and mortality). RESULTS: A severe inflammatory process induced by zymosan administration in WT mice coincided with the damage of lung and small intestine, as assessed by histological examination. Myeloperoxidase activity indicative of neutrophil infiltration and lipid peroxidation were significantly increased in zymosan-treated WT mice. Zymosan in the WT mice also induced a significant increase in the plasma level of nitrite/nitrate. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to ICAM-1 and P-selectin in the lung and intestine of zymosan-treated WT mice. In contrast, the degree of (a) peritoneal inflammation and tissue injury, (b) upregulation/expression of P-selectin and ICAM-1, and (c) neutrophil infiltration were markedly reduced in intestine and lung tissue obtained from zymosan-treated 5-LO deficient mice. Zymosan-treated 5-LOKO showed also a significantly decreased mortality. CONCLUSIONS: These findings clearly demonstrate that 5-LO exerts a role in zymosan-induced nonseptic shock.
Authors: Thomas J H Volman; R Jan A Goris; Michel van der Jagt; Fons A J van de Loo; Thijs Hendriks Journal: Crit Care Med Date: 2002-07 Impact factor: 7.598
Authors: Orhan Veli Ozkan; Oktay Hasan Ozturk; Mehmet Aydin; Nigar Yilmaz; Ibrahim Yetim; Ahmet Nacar; Suleyman Oktar; Sadik Sogut Journal: Curr Ther Res Clin Exp Date: 2010-12
Authors: Peter Andrews; Elie Azoulay; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Geoffrey Dobb; Jean-Yves Fagon; Herwig Gerlach; Johan Groeneveld; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Jerome Pugin; Michael Pinsky; Peter Radermacher; Christian Richard; Robert Tasker; Benoit Vallet Journal: Intensive Care Med Date: 2005-02-18 Impact factor: 17.440
Authors: John C Eun; Ernest E Moore; David C Mauchley; Chris A Johnson; Xianzhong Meng; Anirban Banerjee; Max V Wohlauer; Simona Zarini; Miguel A Gijón; Robert C Murphy Journal: Shock Date: 2012-06 Impact factor: 3.454