Failed antigen presentation after UVB radiation correlates with modifications of Langerhans cell cytoskeleton.
Acute low-dose ultraviolet B radiation (UVR) impairs contact hypersensitivity (CH) induction in genetically defined strains of mice by a mechanism triggered by cis-urocanic acid (UCA) and dependent upon tumor necrosis factor-alpha (TNF-alpha). UVR, TNF-alpha, and cis-UCA cause similar morphologic changes among Langerhans cells, which spawns the speculation that UVR impairs CH induction in part by altering the Langerhans cell cytoskeleton. To examine this speculation, we studied the expression of vimentin in Langerhans cells after treatment with UVR, TNF-alpha, and cis-UCA. All treatments caused a reduction in expression of vimentin within the cytoplasm of Langerhans cells. Because partial loss of detectable vimentin may correlate with cytoskeletal disruption, we evaluated the effects of vinblastine, an agent that disrupts the cytoskeleton by disassembling microtubules, on Langerhans cell density and morphology. Epicutaneous treatment with vinblastine caused a reduction in Langerhans cell density, a loss of dendrites, and a reduction in vimentin expression. When dinitrofluorobenzene was painted on vinblastine-treated skin of BALB/c or C3H/HeN mice, only feeble CH was induced. Consequently, we propose that UVR prevents CH induction in susceptible mice by disrupting the cytoskeleton of Langerhans cells, thereby preventing them from carrying out their crucial role as antigen-presenting cells.
Bacci
S
S
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Nakamura
T
T
Streilein
J W
JW
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene; D007801:Langerhans Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D014747:Vinblastine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; D014747:Vinblastine; D004139:Dinitrofluorobenzene; D014560:Urocanic Acid