SULFITE INDUCES RELEASE OF LIPID MEDIATORS BY ALVEOLAR MACROPHAGES

Air pollutants are supposed to modulate physiological responses of alv eolar macrophages (AM). This study was addressed to the question wheth er at neutral pH sulfur(IV) species in comparison to sulfur(VI) specie s cause AM to release proinflammatory mediators and which pathways are involved in their generation. Supernatants obtained from canine AM tr eated with sulfite (0.1 mM to 2 mM) enhanced the respiratory burst of canine neutrophils, measured by lucigenin-dependent chemiluminescence, whereas supernatants derived from AM treated with sulfate (1 mM) did not. The neutrophil-stimulating activity released by sulfite-treated A M consisted of platelet-activating factor (PAF) and leukotriene B-4 (L TB4) as shown by desensitization of the corresponding receptors. Inhib itors of phospholipase A(2) substantially suppressed release of neutro phil-stimulating activity by sulfite-treated AIM. Inhibition of 5-lipo xygenase in sulfite-treated AM also reduced neutrophil-stimulating act ivity, while inhibition of cyclooxygenase had no effect. In conclusion , sulfite induces AM to release lipid mediators via phospholipase A(2) - and 5-lipoxygenase-dependent pathways. These mediators activate neut rophils via the receptors for PAF and LTB4.