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Involvement of calcium in macrophage leukotriene release during experimental cirrhosis
Author(s) -
Alric L,
Pinelli E,
Carrera G,
Vinel J P,
Beraud M,
Duffaut M,
Pascal J P,
Pipy B
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510230329
Subject(s) - endocrinology , medicine , arachidonic acid , stimulation , zymosan , calcium , cirrhosis , cytosol , leukotriene , secretion , macrophage , chemistry , leukotriene b4 , protein kinase c , biology , inflammation , biochemistry , kinase , enzyme , in vitro , asthma
The aim of the present study was to assess the mechanism of 5‐lipoxygenase metabolites (LT) secretion by peritoneal macrophages in rats wih CC14 induced cirrhosis. After stimulation with calcium ionophore A23187 or opsonized zymosan, [ 3 H] arachidonic acid labeled macrophages from cirrhotic rats presented a significantly greater secretion of LT than macrophages from healthy controls. In addition, the phorbol ester TPA (protein kinase C activator) increased LT production only in macrophages from cirrhotic animals and not in controls. Although Ca 2+ is thought to be involved in 5 lipoxygenase activation, the role of Ca 2+ in LT production was studied. The use of a Ca 2+ ‐free medium as well as the addition of TMB‐8 (an inhibitor of intra‐cellular Ca 2+ movements and of plasma membrane Ca 2+ fluxes) resulted in a fall in LT production greater for macrophages from cirrhotic animals than for controls. The measurement of cytosolic Ca 2+ concentration by cytofluorimetry showed that Fluo‐3 loaded macrophages from cirrhotic rats had a greater cytosolic CA 2+ concentration than macrophages from control animals both in basal conditions and after A23187 stimulation. Study of 45 Ca 2+ uptake suggest, that extra‐cellular Ca 2+ is implicated in the elevated cytosolic Ca 2+ observed in macrophages from cirrhotic animals as compared to healthy controls. The greater Ca 2+ concentration observed in macrophages from cirrhotic rats was not related to a difference in phospholipase C activation because inositol phosphate production did not differ between macrophages from healthy and cirrhotic animals. Taken together these results suggest that as compared to healthy animals, the greater LT production during cirrhosis could be dependent upon a difference in 5‐lipoxygenase activation related to a rise in cytosolic Ca 2+ concentration independently of inositol phosphates generation.