title: Role of 5-lipoxygenase in the multiple organ failure induced by zymosan.
abstract: OBJECTIVE
  This study investigated the role of 5-lipoxygenase in the pathogenesis of multiple organ failure (MOF) induced by zymosan.
  
  
  METHODS
  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.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  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.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy. salvator@unime.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Laura
authors.initials: L
authors.lastname: Dugo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciarra
authors.forename: Angelina
authors.initials: A
authors.lastname: De Sarro
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009102:Multiple Organ Failure / Q000139:chemically induced* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D010538:Peritonitis / Q000139:chemically induced; D011897:Random Allocation; D013577:Syndrome; D015054:Zymosan / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D009569:Nitric Oxide; D015054:Zymosan; D001094:Arachidonate 5-Lipoxygenase