Suppressive effect of exposure to asbestos on cytotoxicity of human NK cells

Nishimura, Yasumitsu

Monday, March 19, 2012: 17:15

Costa Maya 5 (Cancun Center)

Yasumitsu Nishimura, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan

Naoko Kumagai, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan

Megumi Maeda, Division of Bioscience, Department of Biofunctional Chemistry, Okayama University, Graduate School of Natural Science and Technology, Okayama, Japan

Hiroaki Hayashi, Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan

Sehoon Lee, Department of Hygiene, Kawasaki Medical Scool, Kurashiki, Japan

Hidenori Matsuzaki, Department of Hygiene, Kawasaki Medical Scool, Kurashiki, Japan

Kazuya Fukuoka, Respiratory Medicine, Hyogo College of Medicine, Nishinomiya, Japan

Takashi Nakano, Respiratory Medicine, Hyogo College of Medicine, Nishinomiya, Japan

Takumi Kishimoto, Research Center for Asbestos-Related Diseases, Okayama Rosai Hospital, Okayama, Japan

Takemi Otsuki, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan

Introduction
The inhalation of asbestos causes malignant mesothelioma (MM). The mutagenic effect of asbestos is known, whereas its effect on anti-tumor immunity remains unclear. Therefore, the present study examined the effect of asbestos exposure on NK cells.

Methods
We used chrysotile B (CB) asbestos, the cell line of YT-A1, PBMCs and specimens from patients with MM or people positive for pleural plaque (PL), a sign for inhalation of asbestos. Flow cytometry, Bio-plex and realtime PCR were used for NK cell cytotoxicity and cytokine productions.

Results
The analysis for YT-CB5 subline, cultured with CB for 5 months over, showed a decrease in cytotoxicity with low expressions of NKG2D and 2B4. NK cells from MM patients also showed decreased cytotoxicity, accompanied with low expression of NKp46 unlike YT-CB5. The PBMCs cultured with CB for a week resulted in suppressed expression of NKp46 on NK cells, not caused by glass wool, asbestos substitute. The NK cells isolated from CB-exposed PBMCs showed decreased cytotoxicity and low mRNA level of NKp46. The analysis of culture supernatants and cells showed decreases in IL-12 and TNF-α produced by monocyte-lineage cells (MLC) and IFN-γ and IL-17A by Th cells upon exposure to CB. The combined addition of neutralizing antibodies to IL-12, IFN-γ and IL-17A into the culture of PBMCs partially suppressed the level of NKp46 on NK cells. Although cytotoxicity did not differ between PL- and HV-groups, NKp46-low PL-group showed lower cytotoxicity compared with NKp46-high PL-group. Finally, cytotoxicity of NK cells was inversely correlated with the scores of 1, 2 and 3 assigned to NKp46-high PL-, NKp46-low PL- and MM-groups, respectively.

Discussion
These results indicate that exposure to asbestos causes decreased cytotoxicity of NK cells related with low NKp46, partially due to altered production of MCL- or Th-derived cytokines. The diagnosis using NKp46 might contribute to early detection and prevention for MM

A1569 Suppressive effect of exposure to asbestos on cytotoxicity of human NK cells