Inhibition of the respiratory burst and of phagocytosis by nordihydroguaiaretic acid in neutrophils

1. Introduction Leucocytes have an impressive capacity to respond to a variety of stimuli with excitation of random and oriented movements, with secretion of intracellular stored compounds, with an increase in O2 consump- tion and in production of 0; and Hz02. The secretion and the excitation of oxidative metabolism (respiratory burst) are also induced by phagocytosis [l-4]. During the last decade information has accumulated on a series of molecular events that take place at the level of the plasma membrane following the interac- tion with the stimulating agents, this includes changes in transmembrane potential due to modification of Ic’ and Na+ permeability [5-71, modifications of calcium fluxes and disposal [8-l 31, activation of arachidonic acid cascades with generation of prostaglandins, trom- boxanes, leucotrienes and hydroxy fatty acids [ 13-211, modification of cyclic nucleotide turnover [22]. However, the precise nature of the mechanism triggering the manifold responses and the interrela- tion between the various responses remain to be clari- fied. The concept emerging is that oxygenated metabo- lites of arachidonate produced by lipoxygenase, such as monohydroxyeicosatetraenoic acids (HETES), have a role in many leucocyte functions. This view is based on a series of experimental results showing that HETES elicits a chemotactic response in neutrophils [23] and that depletion of arachidonic acid oxygenate products in leucocytes causes an inhibition of random migra- tion and chemotaxis [24], of exocytosis [25,26], of aggregation [27], of calcium influx induced by chemo- tactic peptides [28], and of the respiratory response to chemotactic peptide and digitonin [26,29]. This report presents the effects of nordihydroguai-