Photosensitivity is one of the major symptoms of SLE and related diseases, including subacute CLE and neonatal LE. Although it remains unclear how "photosensitivity" can be examined using laboratory tests, experimental models have been developed and inbred SLE-prone mice have been investigated for a better understanding of the "photosensitivity" phenomenon in relation to autoimmunity (reviewed by Sontheimer 1996).
Natali and Tan (Natali and Tan 1973) first reported experimental skin lesions in mice that resembled SLE. In their experiment, the mice were immunized with UVC-irradiated DNA to produce high titers of circulating antibodies against a DNA photo-product, the thymic dimer. After these mice were whole-body irradiated with UVC, subepidermal immunoglobulin and complement deposition were produced. This result supports the importance of DNA-anti-DNA antibody complexes in the patho-genesis of CLE and the significant influence of UV. However, the role of UVA and UVB irradiation remains obscure because UVC does not reach the earth. The transient occurrence of subepidermal immunoglobulin deposits and macroscopic LE-like lesions was successfully induced in UVB-irradiated rabbits that were previously immunized with heat-denatured DNA (Imamura 1981).
It is well known that patients with LE show hypersensitivity to UVB light (Epstein et al. 1965, Kochevar 1985). In NZB mice, the relationships between autoimmunity, chromosomal abnormalities, and clastogenic factors have been discussed by a few investigators (Emerit 1982, Halpern et al. 1972, Reddy et al. 1978), and the UV sensitivity of NZB cell lines has also been reported (Zamanski et al. 1980). The clastogenic factors were reported to be sensitive to near-UV light (360-400 nm) (Emerit 1982), but the significance of this finding has not been completely understood. B/W F1 mice, which have manifestations more similar to human SLE than NZB mice, produce high serum titers of antinuclear antibodies and anti-DNA antibodies following whole-body irradiation with UVC light (Natali et al. 1978). However, this UV-induced acceleration of autoimmune traits in B/W F1 mice is still controversial (Davis and Percy 1978).
MRL/lpr mice, which have LE-like skin lesions and subepidermal immunoglobu-lin deposits, have yielded us more informative insights into the pathogenesis of UV-related dermatoses than either NZ or BXSB mice, both of which lack macroscopic skin lesions. Long-term exposure to a low dose of UVB radiation accelerates the development of LE-like skin lesions and enhances the intensity of subepidermal immunoglobulin deposits (Horiguchi et al. 1987b). In contrast, UVB irradiation has no effect on the anti-DNA antibody titer of the sera, the incidence of subepidermal immunoglobulin deposits, and the extent of glomerulonephritis (Ansel et al. 1985, Horiguchi et al. 1987b). When subepithelial immunoglobulin deposits in the uteri of MRL/lpr mice are examined after whole-body UVB irradiation, the intensity and incidence of such deposits are not changed, whereas the intensity of these deposits in the skin is enhanced (Furukawa et al. 1986a). Therefore, the promotion of skin lesions in MRL/lpr mice by UVB exposure may not be associated with the acceleration of intrinsic SLE phenomena but rather with reactive changes of the skin against environmental stimuli.
Similar to the susceptible UV-induced cytotoxicity from fibrocytes of NZB mice (Zamanski et al. 1980), fibrocytes and keratinocytes cultured from MRL/lpr mice are susceptible to UVB-induced cytotoxicity (Furukawa et al. 1989). Fibroblasts cultured from newborn MRL/lpr mice show a higher susceptibility to a single UVB light irradiation than MRL/n, F1 hybrids of (MRL/lpr x MRL/n mice) or BALB/c mice. Such susceptibility to UVB irradiation is not observed in young or adult MRL/lpr mice. UVA light irradiation is not cytotoxic. Keratinocytes cultured from MRL mice have a lower cytotoxicity to UVB irradiation than fibroblasts cultured. However, ker-atinocytes from newborn MRL/lpr mice show higher cytotoxicity to relatively low doses of UVB light irradiation than cells from MRL/n mice. Furthermore, syngeneic or allogeneic sera augment the UVB-induced cytotoxicity seen in cultured fibro-blasts. However, UVB irradiation of spleen cells results in no significant difference in cytotoxicity between MRL/lpr mice and MRL/n mice. Unlike the in vivo whole-body irradiation with UVB, susceptibility to UVB light cytotoxicity in vitro may be associated with intrinsic SLE phenomena and may be regulated by the individual's genetic background.
Ansel et al. (Ansel et al. 1985) described the unique effects of broad-spectrum UV irradiation on BXSB mice. UV irradiation increases mortality in BXSB male mice and accelerates autoimmune traits, including anti-DNA antibody production, splenic polyclonal B-cell activity, and glomerulonephritis. These UVB-induced changes in serology and renal function are not observed in MRL/lpr mice (Horiguchi et al. 1987b). In contrast, the macroscopic changes found in MRL/lpr mice are not induced in UVB-irradiated BXSB mice. Therefore, the strain difference between SLE-prone mice irradiated with UV light may serve as useful clues for the investigation of multiple manifestations of photosensitivity in CLE. All SLE-prone mouse strains, in contrast to all non-SLE-prone mouse strains, show increased susceptibility to the induction of DNA damage by UVA and increased DNA synthesis and release after UVA exposure (Golan et al. 1984). Regarding the effects of UVA on SLE symptoms, it is interesting that UVA1 light irradiation decreases clinical disease activity and autoantibodies in patients with human SLE (McGrath 1994).
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