Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line

  • PLoS One. 2014 Jan 20;9(1):e86106. doi: 10.1371/journal.pone.0086106.
Reiji Kojima  1 ,  Tatsukuni Ohno  2 ,  Motoyasu Iikura  3 ,  Toshiro Niki  4 ,  Mitsuomi Hirashima  4 ,  Keichi Iwaya  5 ,  Hitoshi Tsuda  5 ,  Shigeaki Nonoyama  6 ,  Akio Matsuda  2 ,  Hirohisa Saito  2 ,  Kenji Matsumoto  2 ,  Susumu Nakae  7
Affiliations
  • 1. Department of Basic Pathology, National Defense Medical College, Saitama, Japan ; Department of Pediatrics, National Defense Medical College, Saitama, Japan ; Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
  • 2. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
  • 3. Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
  • 4. Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan ; Research Center, GalPharma Company, Takamatsu, Japan.
  • 5. Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
  • 6. Department of Pediatrics, National Defense Medical College, Saitama, Japan.
  • 7. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan ; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan ; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
PMID: 24465902 DOI: 10.1371/journal.pone.0086106
Abstract

Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce Apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of ERK1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI. Gal-9 induced Apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the Other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells.