Variability in bioreactivity linked to changes in size and zeta potential of diesel exhaust particles in human immune cells.
Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used in Europe as diesel fuel additives (Envirox™). We attempted to examine the effects of particles emitted from a diesel engine burning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innate immune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Env were obtained on three separate occasions using identical collection and extraction protocols with the aim of determining the reproducibility of particles generated at different times. However, we observed significant differences in size and surface charge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells and PBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differences in bioreactivity as determined by IL-1β, TNF-α, IL-6, IFN-γ, and IL-12p40 mRNA (by qRT-PCR) and protein expression (by ELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (-37 to -41 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of the bioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expected bioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batch-to-batch variations in physical (and possibly chemical) properties.
Rutgers School of Public Health, Department of Environmental and Occupational Health, Piscataway New Jersey, United States of America.
Srijata
S
Sarkar
Rutgers School of Public Health, Department of Environmental and Occupational Health, Piscataway New Jersey, United States of America.
Lin
L
Zhang
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America.
Prasad
P
Subramaniam
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America.
Ki-Bum
KB
Lee
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America.
Eric
E
Garfunkel
Rutgers School of Public Health, Department of Biostatistics, Piscataway, New Jersey, United States of America.
Pamela A Ohman
PA
Strickland
Department of Environmental Sciences, Rutgers University, New Brunswick, New Jersey, United States of America; Environmental and Occupational Health Sciences Institute Rutgers University, Piscataway, New Jersey, United States of America.
Gediminas
G
Mainelis
Environmental and Occupational Health Sciences Institute Rutgers University, Piscataway, New Jersey, United States of America; Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America.
Paul J
PJ
Lioy
National Heart and Lung Institute, Imperial College, London, United Kingdom.
Teresa D
TD
Tetley
National Heart and Lung Institute, Imperial College, London, United Kingdom.
Kian Fan
KF
Chung
Nicholas School of the Environment and Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America.
Junfeng
J
Zhang
Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.
Mary
M
Ryan
Department of Materials and London Center for Nanotechnology, Imperial College, London, United Kingdom.
Alex
A
Porter
Rutgers School of Public Health, Department of Environmental and Occupational Health, Piscataway New Jersey, United States of America; Environmental and Occupational Health Sciences Institute Rutgers University, Piscataway, New Jersey, United States of America; Rutgers School of Public Health, Center for Global Public Health, Piscataway, New Jersey, United States of America.
Stephan
S
Schwander
D000328:Adult; D002563:Cerium / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D060888:Real-Time Polymerase Chain Reaction; D013499:Surface Properties / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
D016207:Cytokines; D001335:Vehicle Emissions; D002563:Cerium; C030583:ceric oxide