Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression.
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 alpha (TNF-alpha), 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 E(2) 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.
Hart
Prue H
PH
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia. prue.hart@flinders.edu.au
Townley
Scott L
SL
Grimbaldeston
Michele A
MA
Khalil
Zeinab
Z
Finlay-Jones
John J
JJ
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D003877:Dermatitis, Contact / Q000517:prevention & control; D005260:Female; D006632:Histamine / Q000502:physiology*; D007108:Immune Tolerance / Q000528:radiation effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008833:Microcirculation / Q000187:drug effects; D020932:Nerve Growth Factor / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology
D009479:Neuropeptides; D011453:Prostaglandins; D006632:Histamine; D020932:Nerve Growth Factor; D014560:Urocanic Acid; D007213:Indomethacin