Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression
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- 作者：Hart ; Prue H. ; Townley ; Scott L. ; Grimbaldeston ; Michele A. ; Khalil ; Zeinab ; Finlay-Jones ; John J.
- 关键词：cis-Urocanic acid ; Contact hypersensitivity responses ; Rodent
- 刊名：Methods
- 出版年：2002
- 出版时间：September, 2002
- 年：2002
- 卷：28
- 期：1
- 页码：79-89
- 全文大小：268 K
文摘
There is a direct correlation between dermal mast cell prevalence in dorsal skin of different mouse strains and susceptibility to UVB-induced systemic immunosuppression; highly UV-susceptible C57BL/6 mice have a high dermal mast cell prevalence while BALB/c mice, which require considerable UV radiation for 50 % immunosuppression, have a low mast cell prevalence. There is also a functional link between the prevalence of dermal mast cells and susceptibility to UVB- and cis-urocanic acid (UCA)-induced systemic immunosuppression. Mast cell-depleted mice are unresponsive to UVB or cis-UCA for systemic immunosuppression unless they are previously reconstituted at the irradiated or cis-UCA-administered site with bone marrow-derived mast cell precursors. cis-UCA does not stimulate mast cell degranulation directly. Instead, in support of studies showing that neither UVB nor cis-UCA was immunosuppressive in capsaicin-treated, neuropeptide-depleted mice, cis-UCA-stimulated neuropeptide release from sensory c-fibers which, in turn, could efficiently degranulate mast cells. Studies in mice suggested that histamine, and not tumor necrosis factor α (TNF-α), was the product from mast cells that stimulated downstream immunosuppression. Histamine receptor antagonists reduced by approximately 60 % UVB and cis-UCA-induced systemic immunosuppression. Indomethacin administration to mice had a similar effect which was not cumulative with the histamine receptor antagonists. Histamine can stimulate keratinocyte prostanoid production. We propose that both histamine and prostaglandin E2 are important in downstream immunosuppression; both are regulatory molecules supporting the development of T helper 2 cells and reduced expression of type 1 immune responses such as a contact hypersensitivity reaction.