Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.
Exposure to hard metal tungsten carbide cobalt (WC-Co) "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.
Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, West Virginia, United States of America.
Andrea L
AL
Armstead
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Center for Cardiovascular and Respiratory Sciences, Robert C. Byrd Health Sciences Center, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America.
Valerie C
VC
Minarchick
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
Dale W
DW
Porter
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Center for Cardiovascular and Respiratory Sciences, Robert C. Byrd Health Sciences Center, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
Timothy R
TR
Nurkiewicz
Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America; Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, West Virginia, United States of America; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America; Mary Babb Randolph Cancer Center, Morgantown, West Virginia, United States of America.
Bingyun
B
Li
D000818:Animals; D018893:Bronchoalveolar Lavage; D003035:Cobalt / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023382:Toxicity Tests, Acute; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017973:Tungsten Compounds / Q000737:chemistry
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D017973:Tungsten Compounds; C002802:tungsten carbide; D003035:Cobalt