Zinc is required for Fc epsilon RI-mediated mast cell activation.
Zinc (Zn) is an essential nutrient, and its deficiency causes growth retardation, immunodeficiency, and neuronal degeneration. However, the precise roles and molecular mechanism(s) of Zn function in immune response have not been clarified. Mast cells (MCs) are granulated cells that play a pivotal role in allergic reactions and inflammation. The granules of MCs contain various chemical mediators and inflammatory cytokines that are released upon FcepsilonRI cross-linking. In this study, we report that Zn is essential for MC activation both in vitro and in vivo. We showed that a Zn chelator, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine, inhibited in vivo allergic reactions such as PCA and PSA. Consistent with this, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine significantly inhibited the FcepsilonRI-induced degranulation and cytokine production. We found that Zn was required for FcepsilonRI-induced translocation of granules to the plasma membrane, a process that we have shown to be important for MC degranulation. In addition, we showed that Zn was essential for plasma membrane translocation of protein kinase C and subsequent nuclear translocation of NF-kappaB, leading to cytokine production, such as IL-6 and TNF-alpha. These results revealed that Zn was involved in multiple steps of FcepsilonRI-induced MC activation and required for degranulation and cytokine production.
Kabu
Koki
K
Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology (RCAI), Yokohama, Kanagawa, Japan.
Yamasaki
Satoru
S
Kamimura
Daisuke
D
Ito
Yukitaka
Y
Hasegawa
Aiko
A
Sato
Emi
E
Kitamura
Hidemitsu
H
Nishida
Keigo
K
Hirano
Toshio
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000737:chemistry; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005029:Ethylenediamines / Q000737:chemistry; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology; D010766:Phosphorylation; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000502:physiology*
D002614:Chelating Agents; D005029:Ethylenediamines; D016328:NF-kappa B; D017455:Receptors, IgE; D014443:Tyrosine; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium