PMID- 27283431 OWN - NLM STAT- MEDLINE DCOM- 20170313 LR - 20181113 IS - 1743-8977 (Electronic) IS - 1743-8977 (Linking) VI - 13 IP - 1 DP - 2016 Jun 9 TI - Nickel oxide nanoparticles can recruit eosinophils in the lungs of rats by the direct release of intracellular eotaxin. PG - 30 LID - 10.1186/s12989-016-0142-8 [doi] LID - 30 AB - BACKGROUND: Instillation of highly soluble nanoparticles (NPs) into the lungs of rodents can cause acute eosinophilia without any previous sensitizations by the role of dissolved ions. However, whether gradually dissolving NPs can cause the same type of eosinophilia remains to be elucidated. We selected nickel oxide (NiO) as a gradually dissolving NP and evaluated the time course pulmonary inflammation pattern as well as its mechanisms. METHODS: NiO NPs were intratracheally instilled into female Wistar rats at various concentrations (50, 100, and 200 cm(2)/rat) and the lung inflammation was evaluated at various time-points (1, 2, 3, and 4 days). As positive controls, NiCl2 and the ovalbumin-induced allergic airway inflammation model was applied. NiCl2 was instilled at 171.1 mug Ni/rat, which is equivalent nickel concentration of 200 cm(2)/rat of NiO NPs. Cytological analysis and biochemical analysis including lactate dehydrogenase (LDH), total protein, and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). The levels of total immunoglobulin E (IgE) and anaphylatoxins (C3a and C5a) were measured in BALF and serum. The levels of eotaxin were measured in the alveolar macrophages and normal lung tissue before and after addition of cell lysis buffer to evaluate whether the direct lysis of cells can release intracellular eotaxin. RESULTS: NiO NPs produced acute neutrophilic inflammation throughout the study. However, eosinophils were recruited at 3 and 4 days post-instillation of NiO NPs and the magnitude and pattern of inflammation was similar with NiCl2 at 24 h post-instillation. The eosinophil recruitment by NiO NPs was not related with either the levels of total IgE or anaphylatoxins. The lysis of alveolar macrophages and normal lung tissue showed high levels of intracellular eotaxin and the levels of LDH showed positive correlation with the levels of eotaxin. CONCLUSIONS: Instillation of NiO NPs produced neutrophilia at 1 and 2 days after instillation, while the mixed type of neutrophilic and eosinophilic inflammation was produced at 3 and 4 days post-instillation, which was consistent with NiCl2. The mechanism of the eosinophilia involves the direct release of intracellular eotaxin due to the rupture of cells by the accumulated solubilized nickel ions in the phagolysosome. FAU - Lee, Seonghan AU - Lee S AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Hwang, Sung-Hyun AU - Hwang SH AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Jeong, Jiyoung AU - Jeong J AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Han, Youngju AU - Han Y AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Kim, Sung-Hyun AU - Kim SH AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Lee, Dong-Keon AU - Lee DK AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. FAU - Lee, Hae-Suk AU - Lee HS AD - Busan IL Science High School, Busan, Republic of Korea. FAU - Chung, Seung-Tae AU - Chung ST AD - Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Republic of Korea. FAU - Jeong, Jayoung AU - Jeong J AD - Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Republic of Korea. FAU - Roh, Changhyun AU - Roh C AD - Division of Biotechnology Research, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, Republic of Korea. FAU - Huh, Yun Seok AU - Huh YS AD - Department of Biological Engineering, Biohybrid Systems Research Center, Inha University, Incheon, Republic of Korea. FAU - Cho, Wan-Seob AU - Cho WS AD - Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan 2dong, Saha-gu, Busan, 604-714, Republic of Korea. wcho@dau.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160609 PL - England TA - Part Fibre Toxicol JT - Particle and fibre toxicology JID - 101236354 RN - 0 (Chemokines) RN - 7OV03QG267 (Nickel) RN - C3574QBZ3Y (nickel monoxide) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Chemokines/*metabolism MH - Eosinophils/*cytology MH - Female MH - L-Lactate Dehydrogenase/metabolism MH - Lung/cytology/*drug effects MH - Macrophages, Alveolar/drug effects/metabolism MH - Metal Nanoparticles/chemistry/*toxicity MH - Nickel/*chemistry MH - Rats MH - Rats, Wistar PMC - PMC4899890 OTO - NOTNLM OT - Cytotoxicity OT - Eosinophil OT - Eotaxin OT - Nickel oxide nanoparticles OT - Solubility EDAT- 2016/06/11 06:00 MHDA- 2017/03/14 06:00 PMCR- 2016/06/09 CRDT- 2016/06/11 06:00 PHST- 2015/12/11 00:00 [received] PHST- 2016/06/02 00:00 [accepted] PHST- 2016/06/11 06:00 [entrez] PHST- 2016/06/11 06:00 [pubmed] PHST- 2017/03/14 06:00 [medline] PHST- 2016/06/09 00:00 [pmc-release] AID - 10.1186/s12989-016-0142-8 [pii] AID - 142 [pii] AID - 10.1186/s12989-016-0142-8 [doi] PST - epublish SO - Part Fibre Toxicol. 2016 Jun 9;13(1):30. doi: 10.1186/s12989-016-0142-8.