Differential binding of cytokines to environmentally relevant particles: a possible source for misinterpretation of in vitro results?
Inflammation is considered as a key event in adverse health effects associated with exposure to ambient particulate matter. The inflammatory potential of particles is often compared using in vitro cell systems, where the particle-induced release of pro-inflammatory cytokines is measured. A major concern in these assays is the potential of particles to bind cytokines, which may lead to an underestimation of the inflammatory potential. We therefore investigated the cytokine binding to a selection of particle samples, including particles collected from outdoor sources (wood combustion, traffic) and particles commonly used to model environmental sources (ultrafine carbon black, diesel, quartz), for a range of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8). Furthermore, the influence of serum proteins and particle- and cytokine concentrations on the cytokine binding was studied. Cytokines primarily bound to carbonaceous particles (up to 85%), not to mineral particles. Furthermore, depending on the type of cytokine, the cytokine binding could be reduced partly or completely by adding serum proteins to the cell growth medium or particle suspensions. Based on these observations we recommend either to adjust culturing and exposure conditions to prevent cytokine binding, or to adjust the measured cytokine release by application of correction factors obtained from cytokine binding experiments.
Kocbach
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Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway.
Totlandsdal
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Låg
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Refsnes
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Schwarze
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D000327:Adsorption; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D002417:Cattle; D003470:Culture Media / Q000737:chemistry; D004784:Environmental Monitoring / Q000379:methods; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008903:Minerals / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011791:Quartz / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D044967:Serum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000032:analysis / Q000378:metabolism; D012906:Smoke / Q000032:analysis; D053260:Soot / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D001335:Vehicle Emissions / Q000032:analysis; D014934:Wood
D001798:Blood Proteins; D003470:Culture Media; D007378:Interleukins; D008903:Minerals; D052638:Particulate Matter; D011994:Recombinant Proteins; D012906:Smoke; D053260:Soot; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D011791:Quartz; D012710:Serum Albumin, Bovine