title: Respiratory burst in alveolar macrophages exposed to urban particles is not a predictor of cytotoxicity.
abstract: We examined the utility of respiratory burst measurements in alveolar macrophages to assess adverse cellular changes following exposure to urban particles. Cells were obtained by bronchioalveolar lavage of Fisher 344 rats and exposed (0-100 μg/well) to urban particles (EHC-93, SRM-1648, SRM-1649, PM2.5), the soluble (EHC-93sol) and insoluble (EHC-93insol) fractions of EHC-93 (EHC-93tot), mineral particles (TiO(2), SiO(2)) and metal oxides (iron III oxide, iron II/III oxide, copper II oxide, nickel II oxide). The particle-induced respiratory burst was measured by chemiluminescence for 2h after the addition of particles. The cells were then stimulated with phorbol 12-myristate 13-acetate (PMA), yeast Zymosan fragments (Zymosan), or lipopolysaccharide plus interferon-gamma (LPS/IFN-γ) and the stimulant-induced respiratory burst was measured. Independently of the potential of particles to induce directly a respiratory burst, exposure to most particles attenuated the subsequent stimulant-induced burst. The notable exception was SiO(2), which produced a strong respiratory burst upon contact with the macrophages and enhanced the subsequent response to PMA or LPS/IFN-γ. Based on the degree of inhibition of the stimulant-dependent respiratory burst, particles were clustered into groups of high (SRM-1649, iron III oxide), intermediate (EHC-93tot, EHC-93insol, SRM-1648, VERP, iron II/III oxide, copper II oxide), and low (EHC-93sol, SiO(2), TiO2 and nickel II oxide) potency. Across these clusters, the potency of the particles to inhibit the stimulant-dependent respiratory burst showed poor correlation with cytotoxicity determined by XTT reduction assay.
authors: Inhalation Toxicology Laboratory, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada K1A 0K9.
authors: Dalibor
authors: D
authors: Breznan
authors: Patrick
authors: P
authors: Goegan
authors: Vinita
authors: V
authors: Chauhan
authors: Subramanian
authors: S
authors: Karthikeyan
authors: Prem
authors: P
authors: Kumarathasan
authors: Sabit
authors: S
authors: Cakmak
authors: Denis
authors: D
authors: Nadeau
authors: Jeffrey R
authors: JR
authors: Brook
authors: Renaud
authors: R
authors: Vincent
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002947:Cities; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D009573:Nitrites / Q000378:metabolism; D010087:Oxides / Q000633:toxicity; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D016897:Respiratory Burst / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014025:Titanium / Q000633:toxicity; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D008070:Lipopolysaccharides; D009573:Nitrites; D010087:Oxides; D052638:Particulate Matter; C009495:titanium dioxide; D007371:Interferon-gamma; D015054:Zymosan; D014025:Titanium; D013755:Tetradecanoylphorbol Acetate