Functional responses of human neutrophils to sodium sulfite (Na2SO3) in vitro.
An influx of neutrophils into the airways is a common feature observed during pulmonary inflammation induced by air pollutants, including sulfur dioxide and sulfates. In the present study focusing on the in vitro interactions of sodium sulfite (Na2SO3) with human neutrophils, we confirm results indicating that this sulfite induces superoxide production (O2-) by itself. We demonstrated that this response can occur more rapidly than previously reported (within 5 min), and that Na2SO3 can act as a priming agent, in a concentration-dependent fashion, to the bacterial tripeptide N-formyl-methionine-leucine-phenylalanine (fMLP) by increasing O2-production. In addition, our results show that Na2SO3 induces gene expression in human neutrophils in a concentration-dependent manner as assessed by incorporation of 5-[3H] uridine into total RNA. However, it does not induce cell shape changes. We also demonstrated that Na2SO3 does not modulate neutrophil apoptosis nor reverse the well-known delaying effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on apoptosis. We conclude that Na2SO3 acts rapidly on neutrophil physiology, within a few minutes with respect to superoxide production, and a few hours (4 h) with respect to gene expression without altering a biological process such as the rate of apoptosis evaluated after a long period of incubation (20 h). We further conclude that Na2SO3-induced production of O2does not drive neutrophils to undergo apoptosis, a mechanism known to occur in other conditions. Therefore, the potential toxicity of Na2SO3 during pulmonary inflammation or lung-associated diseases may be related to its ability to induce superoxide production without altering neutrophil apoptosis rate.
Labbé
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P
Institut National de la Recherche Scientifique-Santé, Université du Québec, Pointe-Claire, Canada.
Pelletier
M
M
Omara
F O
FO
Girard
D
D
D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D015870:Gene Expression / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects*; D013447:Sulfites / Q000494:pharmacology*; D013481:Superoxides / Q000032:analysis*; D013997:Time Factors
D015415:Biomarkers; D013447:Sulfites; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C025026:sodium sulfite