Suppression of an established immune response by UVA--a critical role for mast cells.
Exposing experimental animals or human volunteers to UVA II (320-340 nm) radiation after immunization suppresses immunologic memory and the elicitation of delayed-in-time hypersensitivity reactions. Previous studies indicated that the mechanisms underlying UVA-induced immune suppression are similar to those described for UVB-induced immune suppression, i.e. transferred by T regulatory cells, overcome by repairing DNA damage, neutralizing interleukin (IL)-10 activity, or injecting recombinant IL-12. Here we continued our examination of the mechanisms involved in UVA II-induced suppression. Antibodies to cis-urocanic acid blocked UVA-induced immune suppression. Treating UVA-irradiated mice with histamine receptor antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists or platelet activating factor receptor antagonists blocked immune suppression in UVA-irradiated mice. In light of the fact that cis-urocanic acid and CGRP target mast cells, which can then release platelet activating factor and histamine, we measured UVA-induced immune suppression in mast cell-deficient mice. No immune suppression was noted in UVA-irradiated mast cell-deficient mice. These findings indicate that exposure to UVA II activates many of the same immune regulatory factors activated by UVB to induce immune suppression. Moreover, they indicate that mast cells play a critical role in UVA-induced suppression of secondary immune reactions.
Ullrich
Stephen E
SE
Department of Immunology and the Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA. sullrich@mdanderson.org
Nghiem
Dat X
DX
Khaskina
Polina
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D014466:Ultraviolet Rays
D006634:Histamine H1 Antagonists; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D015740:Calcitonin Gene-Related Peptide