Association of galectin-9 with eosinophil apoptosis.
BACKGROUND
There is no information whether galectin-9 (a novel eosinophil chemoattractant) was associated with pathogenesis of eosinophilic disorders.


METHODS
We assessed the expression of galectin-9 with imunostaining and in situ hybridization both in the lesion of angiolymphoid hyperplasia with eosinophilia, and peripheral blood eosinophils of eosinophilic patients (E-Eos) in comparison with those of normal volunteers (N-Eos). Regulation of expression of galectin-9 on eosinophils and the effect of galectin-9 on apoptosis of eosinophil were also evaluated.


RESULTS
Many eosinophils infiltrating the site were positive for galectin-9. Surface and intracellular immunoreactive galectin-9 was more evident in E-Eos than N-Eos. When eosinophils were cultured with IL-5 in vitro, the surface galectin-9 expression of E-Eos was significantly downregulated, although that of N-Eos was not affected. Treatment of eosinophils with dexamethasone or anti-Fas antibody significantly upregulated the surface galectin-9 expression of E-Eos. In contrast, dexamethasone partially downregulated the surface galectin-9 of N-Eos, although anti-Fas antibody failed to affect on the surface galectin-9 expression. We also found that recombinant galectin-9 significantly suppressed apoptosis of E-Eos (p = 0.0431), whereas it apparently enhanced apoptosis of N-Eos (p = 0.0173). Furthermore, dexamethasone-induced apoptosis of N-Eos was significantly suppressed by galectin-9 (p = 0.0431), whereas galectin-9 failed to induce significant change in dexamethasone-induced apoptosis of E-Eos. In contrast, apoptosis induced by anti-Fas antibody in both N-Eos (p = 0.0431) and E-Eos (p = 0.0431) was enhanced by galectin-9.


CONCLUSIONS
These findings suggested that galectin-9 was produced by eosinophils, and galectin-9 showed heterogeneous effects and kinetics to eosinophils, and this factor might be one of crucial factors in eosinophilic inflammation.
Saita
Naoki
N
First Department of Internal Medicine, Kumamoto University, School of Medicine, Kumamoto, Japan. saita@gpo.kumamoto-u.ac.jp
Goto
Eisuke
E
Yamamoto
Taro
T
Cho
Isamu
I
Tsumori
Kaori
K
Kohrogi
Hirotsugu
H
Maruo
Keishi
K
Ono
Tomomichi
T
Takeya
Motohiro
M
Kashio
Yumiko
Y
Nakamura
Kazuhiro
K
Hirashima
Mitsuomi
M
D000796:Angiolymphoid Hyperplasia with Eosinophilia / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000276:immunology*; D001706:Biopsy; D003907:Dexamethasone / Q000276:immunology / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D037161:Galectins; D005938:Glucocorticoids / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology; D037102:Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D037161:Galectins; D005938:Glucocorticoids; D015848:Interleukin-5; C105032:LGALS9 protein, human; D037102:Lectins; C411023:anti-Fas monoclonal antibody; D003907:Dexamethasone