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World J Hematol. Nov 6, 2014; 3(4): 128-137
Published online Nov 6, 2014. doi: 10.5315/wjh.v3.i4.128
Granulysin and its clinical significance as a biomarker of immune response and NK cell related neoplasms
Masayuki Nagasawa, Kazuyuki Ogawa, Kinya Nagata, Norio Shimizu
Masayuki Nagasawa, Department of Hematology, Oncology, and Immunology, Tokyo Bay Urayasu/Ichikawa Medical Center, Chiba 279-0001, Japan
Kazuyuki Ogawa, Kinya Nagata, Bio Medical Laboratories Inc., Research and Development Center, Saitama 602-0841, Japan
Norio Shimizu, Tokyo Medical and Dental University, Post Graduate School, Department of Virology, Tokyo 113-8519, Japan
Author contributions: Nagasawa M designed the report; Ogawa K and Nagata K performed the protein analysis; Shimizu N established and provided the cell lines; Nagasawa M analyzed the data and wrote the paper.
Supported by The Grant-in-Aid for Scientific Research from Ministry of Education, Science and Culture Japan, 24591541 to Nagasawa M
Correspondence to: Masayuki Nagasawa, MD, PhD, Department of Hematology, Oncology, and Immunology, Tokyo Bay Urayasu/Ichikawa Medical Center, 3-4-32, Todaijima, Urayasu-city, Chiba 279-0001, Japan. mnagasawa.ped@tmd.ac.jp
Telephone: +81-47-3513101 Fax: +81-47-3526237
Received: October 8, 2013
Revised: February 18, 2014
Accepted: February 20, 2014
Published online: November 6, 2014
Processing time: 268 Days and 1 Hours
Abstract

Granulysin is a cytotoxic granular protein that was identified from human T cells by using the gene subtraction method in 1987. Based on its amino acid homology, granulysin belongs to the saposin-like protein family. The bioactive 9-kDa form of granulysin is processed from the 15-kDa pro-product in the cytoplasmic granules. It is expressed in CD8-positive αβT cells 5 d after mitogenic stimulation and constitutively in natural killer (NK) cells and γδT cells, although regulation of its expression has not yet been precisely determined. The 9-kDa granulysin form has anti-microbial activity against microorganisms such as bacteria, fungi, mycobacteria and parasites, as well as tumoricidal activity against some tumors at 1-10 μmol/L concentrations. Granulysin is secreted in both Ca-dependent and -independent manners. In sera, only the 15-kDa form is detectable and is expected to be a biomarker for immune potency, acute viral infection, anti-tumor immune reaction, acute graft vs host disease, and NK cell associated neoplasm.

Keywords: Granulysin; Saposin-like protein family; Natural killer cell; Cytotoxic T lymphocyte

Core tip: Granulysin is a cytotoxic granular protein expressed in cytotoxic T cells, natural killer (NK) cells and γδT cells, and has anti-microbial activity against microorganisms such as bacteria, fungi, mycobacteria and parasites, as well as tumoricidal activity against some tumors. It is secreted constitutively and in a trigger-dependent manner. Clinically, serum granulysin is a unique biomarker for immune response, immune capacity and NK cell related neoplasms.