Control of mast-cell 5-lipoxygenase

Leukotrienes (LTs) from mast cells make important contributions to early events in inflammation. Therefore, the control of their 5-lipoxygenase was studied. We observed that culture conditions can significantly alter LT synthesis and intracellular 5-lipoxygenase levels. Challenge of mast cells with calcium ionophore A23187 and immunoglobin E (IgE)/antigen had different effects. The calcium ionophore caused continuous LT formation that was accompanied by the translocation of the enzyme to membranes as well as substantial loss of activity. In contrast, with receptor-mediated stimulation, IgE/antigen, enzyme inactivation was insignificant, and membrane binding and LT synthesis were transient. Addition of a calcium chelator stopped ionophore-induced LT production and inactivation of the 5-lipoxygenase and reversed its membrane association. Therefore, receptor-mediated activation of 5-lipoxygenase differs from that by calcium ionophore. The data also indicate that calcium regulates the membrane binding and dissociation of the 5-lipoxygenase. However, with excessively high calcium concentrations activity is lost.