Abstract
The order of potency of retinoids as inhibitors of A23187-induced production of leukotriene B4 (LTB4) in human polymorphonuclear leukocytes (PMN) was retinoic acid > retinal > retinol. However, the conversion of exogenous arachidonate (AA) to LTB4 by PMN homogenates was inhibited in the rank order retinol > retinal ⪢ retinoic acid. The agreement between active concentrations of retinol in these two systems is consistent with this compound acting directly to inhibit AA metabolism: this is not so for the other retinoids. The order of potency for inhibition of phorbol dibutyrate (PDBu)-stimulated superoxide (O−2) production in HL60 granulocytes was retinol > retinoic acid ⪢ retinal (inactive); neither retinol nor retinal displaced [3H]PDBu from HL60 cells. We conclude that inhibition of LTB4 production by retinoic acid and retinal is neither through inhibition of AA metabolism nor through inhibition of protein kinase C.
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