Chronic pulmonary accumulation of iron oxide nanoparticles induced Th1-type immune response stimulating the function of antigen-presenting cells.
Although there is growing evidence that suggests that pulmonary exposure to nanoparticles causes adverse health effects by modulating immune system of the body, available information is very limited. In this study, we investigated immune response following chronic pulmonary accumulation of iron oxide nanoparticles (FeNPs, Fe2O3). FeNPs have a needle-like shape in suspension (101.3±4.2 nm). On day 90 after a single intratracheal instillation (0.5, 1, and 2 mg/kg), the FeNPs remained in the lung and particle-laden macrophages were clearly observed in the BAL fluid of the treated-mice. The number of total cells and proportions of neutrophils and lymphocytes significantly increased at 2 mg/kg dose, and the percentage of apoptotic cells and LDH release increased in a dose-dependent manner. We also found that Th1-polarized inflammatory response was induced in the lung of the treated group accompanying the elevated secretion of chemokines, including GM-CSF, MCP-1, and MIP-1. Additionally, FeNPs enhanced the expression of antigen presentation-related proteins, including CD80, CD86, and MHC class II, on antigen-presenting cells in BAL fluid. Taken together, we suggest that chronic pulmonary accumulation of FeNPs may induce Th1-polarized immune response augmenting the function of antigen-presenting cells in the lung.
Myunggok Eye Research Institute, Konyang University, 685, Gasuwon-dong, Seo-Gu, Daejeon 302-718, Republic of Korea. Electronic address: pejtoxic@hanmail.net.
Eun-Jung
EJ
Park
Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, Republic of Korea.
Seung Yun
SY
Oh
Inhalation Toxicology Center, Korea Institute of Toxicology, Jeongeup 580-185, Republic of Korea.
Sang Jin
SJ
Lee
Inhalation Toxicology Center, Korea Institute of Toxicology, Jeongeup 580-185, Republic of Korea.
Kyuhong
K
Lee
Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, Republic of Korea.
Younghun
Y
Kim
Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon, Republic of Korea.
Byoung-Seok
BS
Lee
Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, Canada.
Jong Sung
JS
Kim
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D005434:Flow Cytometry; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D008297:Male; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013499:Surface Properties; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D059467:Transcriptome
D016207:Cytokines; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
Antigen-presentation; Dendritic cells; Immunotoxicity; Iron oxide nanoparticles; Macrophages; Pulmonary inflammation