ABSTRACT
The purpose of this study was to elucidate the mechanism of the airborne poultry dust (particulate matter, PM)-induced respiratory tract inflammation, a common symptom in agricultural respiratory diseases. The study was based on the hypothesis that poultry PM would induce the release of inflammatory cytokine interleukin-8 (IL-8) by respiratory epithelial cells under the upstream regulation by cytosolic phospholipase A2 (cPLA2) activation and subsequent formation of cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites (eicosanoids). Human lung epithelial cells (A549) in culture were treated with the poultry PM (0.1-1.0 mg) for different lengths of time, following which PLA2 activity, release of eicosanoids and secretion of IL-8 in cells were determined. Poultry PM (1.0 mg/ml) caused a significant activation of PLA2 in a time-dependent manner (15-60 min), which was significantly attenuated by the calcium-chelating agents, cPLA2-specific inhibitor (AACOCF3) and antioxidant (vitamin C) in A549 cells. Poultry PM also significantly induced the release of COX- and LOX-catalyzed eicosanoids (prostaglandins, thromboxane A2 and leukotrienes B4 and C4) and upstream activation of AA LOX in the cells. Poultry PM also significantly induced release of IL-8 by the cells in a dose- and time-dependent manner, which was significantly attenuated by the calcium chelating agents, antioxidants and COX- and LOX-specific inhibitors. The current study for the first time revealed that the poultry PM-induced IL-8 release from the respiratory epithelial cells was regulated upstream by reactive oxygen species, cPLA2-, COX- and LOX-derived eicosanoid lipid signal mediators.
Subject(s)
Agriculture , Animals , Antioxidants/pharmacology , Arachidonic Acid/metabolism , Arachidonic Acid/metabolism , Biocatalysis , Cell Line , Cytokines/metabolism , Dose-Response Relationship, Drug , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Eicosanoids/metabolism , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Humans , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-8/metabolism , Lipoxygenases/metabolism , Particulate Matter/chemistry , Particulate Matter/pharmacology , Phospholipases A2, Cytosolic/antagonists & inhibitors , Phospholipases A2, Cytosolic/metabolism , Poultry , Prostaglandin-Endoperoxide Synthases/metabolism , Reactive Oxygen Species/metabolism , Respiratory Mucosa/cytology , Respiratory Mucosa/metabolism , Respiratory Mucosa/metabolism , Signal Transduction/drug effects , Solvents/chemistry , Time FactorsABSTRACT
Experimental acute sinusitis was induced in 21 New Zealand hybrid rabbits by occluding the ostium and inoculating them with Streptococcus pneumonia. While a group of rabbits with sinusitis was left untreated, two other groups were administered parenteral sodium nitroprussid (SNP) and oral levofloxacin for ten days. While staphylococci species, non-hemolytic streptococcus and contaminated flora were isolated from the sinuses of controls, Streptococcus pneumonia was re-isolated in two of six untreated rabbits, in one of six SNP administered rabbits and none of the levofloxacin treated rabbits. Serum and maxillary sinus mucosal nitric oxide (NO) levels were correlated. While the mean maxillary sinus NO level of controls was significantly higher than that of untreated rabbits, the mean maxillary sinus and serum NO levels were significantly higher in SNP administered rabbits than in the others. Although goblet cell hyperplasia and squamous cell metaplasia were detected in some slides, edema and neutrophil infiltration were the prominent findings. The most severe inflammatory changes were found in the untreated sinusitis group on the third and fifth days. The earliest improvement was observed in the levofloxacin treated rabbits. It was concluded that NO level is decreased during acute sinusitis and that SNP administration hastens the bacteriological and histological recovery.