Chloroquine interaction with inflammatory human polymorphonuclear leucocytes.

The molecular in vitro association of radiolabelled chloroquine (CQ) with both normal resting and inflammatory polymorphonuclear leucocytes (PMNs) was measured. For this purpose a suitable ligand-association assay was developed to measure the cell association and the intracellular concentration of CQ. Under the influence of inflammatory stimuli PMNs display altered interaction with CQ. The intracellular concentration of CQ is reduced with 30 to 40% under inflammatory (disease) states when compared with non-inflammatory conditions. The mechanisms of CQ-PMN interaction associated with these altered intracellular concentrations of CQ are considered, with particular attention to the effects of rheumatic disease. Association experiments of CQ with PMNs performed in the presence of different established transport inhibitors showed that both diffusive uptake and carrier-mediated transport are involved in the cell accumulation of CQ in inflammatory PMNs. From these results, emphasis is given to three explanations for the decrease of the intracellular CQ concentration in inflamed PMNs. a) the expansion of the PMN volume under inflammatory conditions; b) the cytoplasmic or lysosomal pH changes and activation of the PMN Na+/H+ antiport by inflammatory stimuli; and c) the exocytic release of the granules (degranulation). Our data suggest that all these mechanisms, based on the events involved in inflammatory responses, may be involved in the decrease of the intracellular CQ concentration in inflammatory PMNs.