Reactive oxygen intermediates and eicosanoid production by kupffer cells and infiltrated macrophages in acute and chronic liver injury induced in rats by CCl4.
OBJECTIVE
The aim of the present study was to characterize during acute and chronic liver injury induced by CCl4, macrophage phenotypes and whether a change in reactive oxygen intermediates (ROI) and eicosanoids production by Kupffer cells (KC) was observed.


METHODS
Liver steato-necrosis and cirrhosis were induced in rats after 3 weeks and 9 weeks of CCl4 intoxication, respectively. Monocytes and tissue macrophages were identified by immunohistochemical study using monoclonal antibodies ED-1 and tissue macrophages using the antibody ED-2. The release of ROI and eicosanoids in response to the phorbol ester TPA (protein kinase activator) and to the calcium ionophore A23187 was assessed in cultivated cells.


RESULTS
As compared to healthy controls, livers of rats with steato-necrosis or cirrhosis exhibited a significant increase of ED-1 and ED-2 positive cells. Only KC from rats with liver steato-necrosis were found to have higher A23187, TPA + A23187 or opsonized zymosan induced ROI production than healthy controls (p < 0.01). After TPA + A23187 or opsonized zymosan stimulation, KC from both rats with steato-necrosis or cirrhosis produced more TxB2 and leukotrienes and less PGE2 as compared to healthy controls (p <0.05).


CONCLUSIONS
These results suggest an influx of monocytes into the liver during acute and chronic injury induced by CCl4. Functional changes of this inflammatory infiltrate have been demonstrated with an increase of ROI production only in the early stage of liver injury whereas a rise in KC leukotriene production and an imbalance between cytoprotective and cytotoxic prostanoids were observed at all stages of liver disease.
Alric
L
L
Laboratoire UPRES-EA-2405 Macrophages, médiateurs de l'inflammation et interactions cellulaires, Hopital Rangueil, 31054 Toulouse, France. alric.1@chu-toulouse.fr
Orfila
C
C
Carrere
N
N
Beraud
M
M
Carrera
G
G
Lepert
J C
JC
Duffaut
M
M
Pipy
B
B
Vinel
J P
JP
D000208:Acute Disease; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D002908:Chronic Disease; D015777:Eicosanoids / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D015777:Eicosanoids; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D013929:Thromboxane B2; D001094:Arachidonate 5-Lipoxygenase