EFFECTS OF ORGANOMETALS ON CELLULAR SIGNALING .2. INHIBITION OF REINCORPORATION OF FREE ARACHIDONIC-ACID AND INFLUENCE ON PAF-ACETHER SYNTHESIS BY TRIETHYLLEAD

Organometal compounds affect many enzymes, especially those containing SH-groups as acyl- and acetyltransferases involved in lysophospholipi d reacylation. In HL-60 cells, organotin and -lead compounds stimulate phospholipase A(2) activity, contributing thus to increase the lever of lysophospholipids In the present study, we have tested whether paf- acether (paf) biosynthesis was affected by treatment with triethyllead (Et(3)PbCl) in HL-60 cells. Et(3)PbCl inhibits the incorporation of e xogenous arachidonic acid in the presence of high (greater than or equ al to 50 mu M) but not low concentrations (less than or equal to 1 mu M). High concentrations of the lead compound are unable to induce oaf formation by itself, however, lower concentrations (less than or equal to 10 mu M) acted synergistically with TPA or fMLP to stimulate oaf f ormation. Whereas unstimulated cells produced 0.4 pmole paf/2 x 10(6) cells, the stimulation with low fMLP (0.1 mu M) resulted in the synthe sis of 1.7 pmole and with low TPA (2 ng/ml) in 0.5 pmole paf. Preincub ation of the cells with 10 mu M Et(3)PbCl for 20 to 30 min increased t he amount of paf formed by these cells to 3.3 pmole after treatment wi th 0.1 mu M fMLP and 1.5 pmole after TPA. Furthermore, the results sho wed an inhibition of acetyltransferase (the key enzyme of paf synthesi s) by the high and not by low concentrations of the lead compound. We conclude that low concentrations of Et(3)PbCl (less than or equal to 1 0 mu M) may act as a synergistic inducer of paf synthesis initiated vi a a receptor-coupled stimulation.