Role of 5-lipoxygenase in the multiple organ failure induced by zymosan.
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.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy. salvator@unime.it
Rossi
Antonietta
A
Serraino
Ivana
I
Di Paola
Rosanna
R
Dugo
Laura
L
Genovese
Tiziana
T
Britti
Domenico
D
Sciarra
Giuseppe
G
De Sarro
Angelina
A
Caputi
Achille P
AP
Sautebin
Lidia
L
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*
D009569:Nitric Oxide; D015054:Zymosan; D001094:Arachidonate 5-Lipoxygenase