Peptides of major basic protein and eosinophil cationic protein activate human mast cells

Hiroyuki Ogasawara; Masahiro Furuno; Koji Edamura; Masato Noguchi

doi:10.1016/j.bbrep.2019.100719

Peptides of major basic protein and eosinophil cationic protein activate human mast cells

Biochem Biophys Rep. 2019 Dec 25:21:100719. doi: 10.1016/j.bbrep.2019.100719. eCollection 2020 Mar.

Authors

Hiroyuki Ogasawara¹, Masahiro Furuno¹, Koji Edamura¹, Masato Noguchi¹

Affiliation

¹ Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-13-2 Fukuura, Kanazawa-Ku, Yokohama, Kanagawa, 236-0004, Japan.

Abstract

The eosinophil granule proteins, major basic protein (MBP) and eosinophil cationic protein (ECP), activate mast cells during inflammation; however the mechanism responsible for this activity is poorly understood. We found that some theoretical tryptase-digested fragments of MBP and ECP induced degranulation of human cord blood-derived mast cells (HCMCs). The spectrum of activities of these peptides in HCMCs coincided with intracellular Ca²⁺ mobilization activities in Mas-related G-protein coupled receptor family member X2 (MRGPRX2)-expressing HEK293 cells. Two peptides corresponding to MBP residues 99-110 (MBP (99-110)) and ECP residues 29-45 (ECP (29-45)), respectively, induced degranulation of HCMCs and intracellular Ca²⁺ mobilization in MRGPRX2-expressing HEK293 cells in a concentration-dependent manner. Stimulation with MBP (99-110) or ECP (29-45) induced the production of prostaglandin D2 by HCMCs. The activities of MBP (99-110) and ECP (29-45) in both HCMCs and MRGPRX2-expressing HEK293 cells were inhibited by MRGPRX2-specific antagonists. In conclusion, these results indicated that MBP and ECP fragments activate HCMCs, and it may occur via MRGPRX2. Our findings suggest that tryptase-digested fragments of eosinophil cationic proteins acting via the MRGPRX2 pathway may further our understanding of mast cell/eosinophil communication.

Keywords: Cationic peptide; ECP; ECP, eosinophil cationic protein; GPCR, G protein-coupled receptor; HCMC, human cord blood-derived mast cell; MBP; MBP, major basic protein; MC, mast cell; MRGPRX2; MRGPRX2, Mas-related G protein-coupled receptor X2; Mast cell/eosinophil communication; PGD2, prostaglandin D2; Tryptase.