P. Dieter et E. Fitzke, FORMATION OF DIACYLGLYCEROL, INOSITOL PHOSPHATES, ARACHIDONIC-ACID AND ITS METABOLITES IN MACROPHAGES, European journal of biochemistry, 218(2), 1993, pp. 753-758
Treatment of macrophages with zymosan, 4beta-phorbol 12-myristate 13-a
cetate (PMA) and fluoride but not with A 23187 or arachidonic acid (DE
LTAAch) leads to a generation of diacylglycerol (acyl2Gro). Formation
of inositol phosphates is achieved with zymosan, only. An elevation of
intracellular calcium is obtained with zymosan and A 23187 but not wi
th PMA, fluoride or DELTAAch. Prior treatment of the cells with phorbo
l ester for 3 h which has been shown recently to result in a down-regu
lation of protein kinase (PK) C-beta but not PKC-delta [Duyster, J., S
chwende, H., Fitzke, E., Hidaka H. & Dieter P. (1993) Biochem. J. 292,
203-207] has no effect on the zymosan-induced formation of acyl2Gro o
r inositol phosphates but inhibits the PMA-induced generation of acyl,
Gro. Down-regulation of PKC-delta by prior phorbol ester treatment for
24 h augments the zymosan-induced generation of acyl2Gro and inositol
phosphates. The acyl2Gro lipase inhibitor RG 80267 inhibits the PMA-i
nduced and fluoride-induced generation of prostaglandin (PG) E2, reduc
es the zymosan-induced release of PGE, by 50% but has no effect on PGE
, formation of unstimulated, A 23187-treated or DELTAAch-treated cells
. Furthermore, RG 80267 enhances accumulation of DELTAAch-labeled acyl
,Gro in response to zymosan, PMA and fluoride. These data indicate tha
t zymosan activates a phosphatidylinositol 4,5-bisphosphate-specific p
hospholipase (PL) C, that generation of acyl2Gro by PMA and fluoride o
ccurs via hydrolysis of other phospholipids, that PKC-beta is involved
in the PMA-induced generation of acyl2Gro and PKC-delta negatively mo
dulates the zymosan-induced activation of PLC and PMA and fluoride ind
uce a liberation of DELTAAch from acyl2Gro, A 23187 activates the PLA2
pathway and zymosan stimulates both, the acyl2Gro- and PLA2-pathway.