Activation of Human Neutrophils by the Air Pollutant Sodium Sulfite (Na2SO3): Comparison with Immature Promyelocytic HL-60 and DMSO-Differentiated HL-60 Cells Reveals That Na2SO3 Is a Neutrophil but Not a HL-60 Cell Agonist

Sulfite exposure can induce inflammatory responses characterized by an influx of neutrophils into the airways leading to lung malfunctions. Studies focusing on sodium sulfite (Na2SO3)/neutrophil interactions have shown that this chemical possesses proinflammatory properties based on its ability to induce a respiratory burst. Information regarding how this chemical could alter other neutrophil responses/functions as well as its role on immature promyelocytic cells is currently lacking in the literature. In this study, we report that Na2SO3 can induce tyrosine phosphorylation events in human neutrophils but not in both HL-60 and HL-60 + DMSO. As a positive control, GM-CSF was found to induce tyrosine phosphorylation of a particular protein of 120–130 kDa in both HL-60 and HL-60 + DMSO cells testifying that these cells were responsive. In addition, we report that Na2SO3 does not alter neutrophil phagocytosis and that this chemical increases the release of the proinflammatory cytokine IL-8 but not TNF-α. Paradoxically, we found that Na2SO3 acts as a potent inhibitor of de novo neutrophil protein synthesis in a concentration-dependent fashion (0.1, 1, or 10 mM) as assessed by SDS–PAGE from metabolically [35S]-labeled cells. In contrast to mature neutrophils, we found that Na2SO3 does not modulate de novo protein synthesis in HL-60 cells treated with low concentrations (0.1 or 1 mM) and that this pollutant was toxic at 10 mM as judged by a drastic decrease of total protein content stained with Coomassie blue. We conclude that Na2SO3 can activate human neutrophils and that its proinflammatory potential is further supported by its ability to increase IL-8 production. In addition, our results clearly indicate that HL-60 and HL-60 + DMSO respond differently than mature human neutrophils to the inflammatory pollutant Na2SO3. Extrapolation of data obtained with HL-60 (and/or HL-60 + DMSO) to neutrophils should be taken with caution. Our data obtained with Na2SO3 are an example.