Inhibition of mast cell degranulation by melanin

Yoshiyuki Kawamoto, Hiromoto Kondo, Mari Hasegawa, Chiharu Kurimoto, Yuuki Ishii, Chihiro Kato, Taishi Botei, Muneshige Shinya, Takashi Murate, Yuki Ueno, Masao Kawabe, Yuko Goto, Ryohei Yamamoto, Machiko Iida, Ichiro Yajima, Nobutaka Ohgami, Masashi Kato, Kozue Takeda

Research output: Contribution to journalArticle

Abstract

Melanin is a dark naturally occurring pigment produced in nature and in many organisms. Although several reports have demonstrated applications for melanins in various therapeutic treatments, to date, no research has examined the anti-allergic effect of melanin. In this study, we for the first time found that solubilized or synthesized soluble melanin acts as a potent inhibitor of the degranulation of mast cells. We found that squid-ink-derived melanin significantly inhibited antigen-IgE-FcεRI-mediated degranulation of the mucosal mast cell line RBL-2H3. A homogenized melanin nanoparticle prepared by laser ablation also clearly suppressed antigen-induced mast cell degranulation. We also successfully solubilized synthetic melanin in a neutral biochemical buffer and found that it also significantly inhibited IgE-sensitized mast cells. The anti-degranulation activity of synthesized melanin was abolished in the melanin fraction below 50-kD molecular weight. All melanins used in this study did not exert significant cell death. Signal transduction analysis revealed that melanin suppressed antigen-triggered phosphorylation of signaling molecules as well as calcium influx. Transmission electron microscopy revealed that homogenized melanin nanoparticles partially attached to the cell surface and some nanoparticles were internalized to the cell. Flow cytometry revealed that the number of FcεRI-bound IgE molecules was decreased by melanin. Fluorescence recovery after photobleaching analysis indicated that melanin attenuated both plasma membrane and cytoplasmic fluidity, implying that melanin increased their viscosities. In vivo experiments using passive systemic anaphylaxis (PSA) and passive cutaneous anaphylaxis (PCA) mouse models demonstrated that oral administration of melanin accelerated the recovery of decreased body temperature after antigen infection in PSA, and combination sensitization of IgE with melanin attenuated antigen-induced extravasation in PCA. These findings indicated that melanin exhibits preventative effects against IgE-mast cell-mediated anaphylaxis. This study provides the first evidence that homogenized melanin may be a potential therapeutic agent for diseases involving mast cells.

Original languageEnglish
Pages (from-to)178-193
Number of pages16
JournalBiochemical Pharmacology
Volume163
DOIs
Publication statusPublished - 2019 May 1
Externally publishedYes

Fingerprint

Melanins
Immunoglobulin E
Antigens
Nanoparticles
Recovery
Photobleaching
Anti-Allergic Agents
Signal transduction

Keywords

  • Allergy
  • Degranulation
  • Hypersensitivity
  • Mast cell
  • Melanin
  • Sepia

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Kawamoto, Y., Kondo, H., Hasegawa, M., Kurimoto, C., Ishii, Y., Kato, C., ... Takeda, K. (2019). Inhibition of mast cell degranulation by melanin. Biochemical Pharmacology, 163, 178-193. https://doi.org/10.1016/j.bcp.2019.02.015

Inhibition of mast cell degranulation by melanin. / Kawamoto, Yoshiyuki; Kondo, Hiromoto; Hasegawa, Mari; Kurimoto, Chiharu; Ishii, Yuuki; Kato, Chihiro; Botei, Taishi; Shinya, Muneshige; Murate, Takashi; Ueno, Yuki; Kawabe, Masao; Goto, Yuko; Yamamoto, Ryohei; Iida, Machiko; Yajima, Ichiro; Ohgami, Nobutaka; Kato, Masashi; Takeda, Kozue.

In: Biochemical Pharmacology, Vol. 163, 01.05.2019, p. 178-193.

Research output: Contribution to journalArticle

Kawamoto, Y, Kondo, H, Hasegawa, M, Kurimoto, C, Ishii, Y, Kato, C, Botei, T, Shinya, M, Murate, T, Ueno, Y, Kawabe, M, Goto, Y, Yamamoto, R, Iida, M, Yajima, I, Ohgami, N, Kato, M & Takeda, K 2019, 'Inhibition of mast cell degranulation by melanin', Biochemical Pharmacology, vol. 163, pp. 178-193. https://doi.org/10.1016/j.bcp.2019.02.015
Kawamoto Y, Kondo H, Hasegawa M, Kurimoto C, Ishii Y, Kato C et al. Inhibition of mast cell degranulation by melanin. Biochemical Pharmacology. 2019 May 1;163:178-193. https://doi.org/10.1016/j.bcp.2019.02.015
Kawamoto, Yoshiyuki ; Kondo, Hiromoto ; Hasegawa, Mari ; Kurimoto, Chiharu ; Ishii, Yuuki ; Kato, Chihiro ; Botei, Taishi ; Shinya, Muneshige ; Murate, Takashi ; Ueno, Yuki ; Kawabe, Masao ; Goto, Yuko ; Yamamoto, Ryohei ; Iida, Machiko ; Yajima, Ichiro ; Ohgami, Nobutaka ; Kato, Masashi ; Takeda, Kozue. / Inhibition of mast cell degranulation by melanin. In: Biochemical Pharmacology. 2019 ; Vol. 163. pp. 178-193.
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