Ultraviolet light and lysosome activity

The abdominal skin of guinea pigs was irradiated by a Xenon short arc lamp with glass filters. Acid phosphatase and beta-glucuronidase activity increased in the irradiated skin. The change of acid phosphatase is slow and mild in intensity, while that of beta-glucuronidase is quick and high in degree. The activity of acid phosphatase is influenced equally by light with filters of UV-25, UV-27, UV-29, and UV-31, while that of beta-glucuronidase is affected more mildly by light with a UV-31 filter than with any of the other three filters. These findings suggest that there is a close relationship between cutaneous changes induced by ultraviolet light and changes in lysosome activity, and that energy required to induce changes in enzyme activity is much less than energy required to produce erythema.     

Blue light irradiation suppresses dendritic cells activation in vitro

Blue light is a UV‐free irradiation suitable for treating chronic skin inflammation, for example, atopic dermatitis, psoriasis, and hand‐ and foot eczema. However, a better understanding of the mode of action is still missing. For this reason, we investigated whether dendritic cells (DC) are directly affected by blue light irradiation in vitro. Here, we report that irradiation neither induced apoptosis nor maturation of monocyte‐derived and myeloid DC. However, subsequent DC maturation upon LPS/IFNγ stimulation was impaired in a dose‐dependent manner as assessed by maturation markers and cytokine release. Moreover, the potential of this DC to induce cytokine secretion from allogeneic CD4 T cells was reduced. In conclusion, unlike UV irradiation, blue light irradiation at high and low doses only resulted in impaired DC maturation upon activation and a reduced subsequent stimulatory capacity in allogeneic MLRs with strongest effects at higher doses.     

Ultraviolet light and epidermal immunologic phenomena

It is well known that ultraviolet (UV) irradiation may alter the immunological reactivity of an experimental animal in such a manner that a state of antigen-specific immune suppression is induced. Although there exist several attractive hypotheses for this UV-induced immune suppression, its exact mode of generation has yet to be clarified. Since the skin represents the only natural target organ for UV, one may assume that the signals which lead to UV-induced immune suppression originate in the skin itself. This assumption is supported by the findings that the skin harbors a variety of immunoactive cells which are critically needed for mounting a T-cell-dependent immune response and whose functional capacity can be impaired by UV irradiation. The detailed analysis of molecular events operative in UV-induced immunosuppression may add to our understanding of mechanisms and prevention of photocarcinogenesis but also bears important clinical implications for the fields of environmental und preventive medicine.     

Ultraviolet light hardening in polymorphous light eruption--a controlled study comparing different emission spectra.

Polymorphous light eruption (PLE) is a common disorder characterized by a delayed, abnormal response to ultraviolet (UV) radiation, with a varied morphology of itching efflorescences on sun-exposed areas of the skin. Thirty-one PLE subjects were treated with either UVA (340-400 nm) or UVA and UVB (300-400 nm) phototherapy during spring 1987 (10 exposures to UV light). They were randomly allocated to these 2 groups. For subjects of the UVA group, the applied dose corresponded to their individual minimal tanning dose; for subjects of the UVA and UVB group it corresponded to approximately 3/4 of their individual minimal erythema dose. The sun protection effect was studied by a high dose of UVA (80-160 J/cm2; 340-440 nm) after the treatment period, by analysing the histidine content of the stratum corneum and the urocanic acid photoisomerization, and by evaluating the subjects' diaries. The patients were asked to expose their skin to sunlight at least 3 times after UV hardening in the following 2-10 weeks. The results of both the UVA provocation and of the natural sun exposure confirmed the success of UV hardening without the occurrence of severe side effects. The content of histidine and of its metabolite urocanic acid in stratum corneum was significantly increased during the treatment. These data are interpreted to be biochemical markers for improved sun protection.     

Ultraviolet light therapy in chronic urticaria

Fifteen patients with chronic urticaria were treated with ultraviolet light B (UVB) for 1-3 months during the spring 1984 and a follow-up study was performed in November 1984-January 1985. Patients with cold urticaria, cholinergic urticaria and dermographism became clearly better or got rid of their symptoms more often than those with "non-specific" chronic urticaria. The good results achieved during the phototherapy held during the summer but in the autumn urticaria became worse in one third of the cases. The result suggests that UV-therapy might be worth trying in many patients with chronic urticaria.     

Ultraviolet B radiation suppresses endocytosis, subsequent maturation, and migration activity of langerhans cell-like dendritic cells

Langerhans cells capture exogenous antigens through fluid phase pinocytosis and receptor-mediated endocytosis and migrate to lymph nodes, where they present processed antigen to T cells. Ultraviolet B radiation impairs the antigen-presenting function of Langerhans cells, resulting in antigen-specific immunosuppression of contact hypersensitivity. We tested the notion that ultraviolet B radiation inhibits the endocytic activity of Langerhans cells, leading to impaired migration and maturation. Human monocyte-derived Langerhans cell-like dendritic cells that took up lucifer yellow or fluorescein isothiocyanate dextran exclusively migrated in response to 6Ckine/secondary lymphoid chemokine, and matured, as evidenced by an increase in CD54 and CD86 expression and potent stimulatory activity in allogeneic mixed lymphocyte reaction. Exposing Langerhans cell-like dendritic cells to 20-40 mJ per cm2 of ultraviolet B radiation reduced their endocytic activity in fluid phase pinocytosis (measured by uptake of lucifer yellow) and in receptor-mediated endocytosis (measured by uptake of fluorescein isothiocyanate dextran). Membrane ruffling and CD32 expression were also suppressed by ultraviolet B radiation. Ultraviolet B-irradiated, endocytosing Langerhans cell-like dendritic cells had less movement towards 6Ckine, expressed less CD54 and CD86, and had less effective stimulatory activity in allogeneic mixed lymphocyte reaction than nonirradiated, endocytosing Langerhans cell-like dendritic cells. Endocytosis upregulated tumor necrosis factor alpha production by Langerhans cell-like dendritic cells, but prior ultraviolet B radiation inhibited this enhancement. These data suggested that impaired endocytosis and subsequent inhibitory migration and maturation of Langerhans cells by ultraviolet B radiation could contribute to local immunosuppression of contact hypersensitivity.     

Plasmacytoid dendritic cells are absent in skin lesions of polymorphic light eruption

BACKGROUND/PURPOSE: Polymorphic light eruption (PLE) is a common photodermatosis of potential autoimmune origin, and an overlap with lupus erythematosus (LE) has been described. Plasmacytoid dendritic cell (PDC)-induced expression of interferon (IFN)-alpha has been found to be present in LE skin lesions and plays a pivotal role in the pathogenesis of LE by promoting autoimmunity. We therefore asked whether PDCs may also be involved in the pathogenesis of PLE and searched for those cells [which can be identified by their high levels of interleukin (IL)-3 receptor alpha chain (CD123), combined with other cell markers such as CD68] in skin lesions. METHODS: Paraffin-embedded biopsy specimens from a total of 27 patients with clinically and histologically confirmed PLE (nine women, mean age 32.7 years, age range 18-43), LE (seven women, four men, CCLE: n=4, SCLE: n=2, lupus tumidus: n=5, mean age 48.5 years, age range 41-65) or psoriasis (four women, three men, mean age 43.3 years, age range 19-54) (as control group) were analyzed by immunohistochemical CD68/CD123 double staining. Quantification of the immunohistochemical staining was performed by visual cell counting of CD68-/CD123+, CD68+/123-, and CD68+/CD123+ cells separately in the epidermis and dermis of the samples in at least 10 random fields per sample at x 400 microscopic magnification by two of the investigators in a blinded fashion. RESULTS: Microscopic examination of the immunohistochemically stained sections revealed that CD68+/CD123+ cells were present in most specimens obtained from LE [10/11 (91%)] and psoriasis [6/7 (86%)] patients but not at all in those obtained from PLE patients. Quantification and statistical analysis of the dermal infiltrate revealed that CD68+/CD123+ cells were present at a mean+/-SEM field density of 5.6+/-1.3 in LE, 1.6+/-0.6 in psoriasis but totally absent in PLE (P=0.0010 vs. LE, P=0.0135 vs. psoriasis by an unpaired Student's t-test). CONCLUSION: The results confirm the potential significance of PDCs in LE and psoriasis, however the absence of PDCs in PLE contradicts the hypothesis that these cells might play a role in the latter disease.     

Ultraviolet protective eyewear for Wood's light use

When interpreting delayed patch test reads for children suspected of having contact dermatitis, we use the Wood's light to illuminate the highlighter outlines we made at the first read. Our pediatric patients wear single-use ultraviolet protective goggles to shield their retinas, because children have a propensity to attempt to look into the Wood's lamp.     

Ultraviolet B radiation and reactive oxygen species modulate interleukin-31 expression in T lymphocytes, monocytes and dendritic cells

Background Interleukin (IL)‐31 is a novel Th2 T‐cell cytokine that induces pruritus and dermatitis in transgenic mice. While enhanced mRNA expression of this cytokine is detected in skin samples of inflammatory skin diseases, the regulation of IL‐31 expression is poorly understood. Objectives To assess the effects of ultraviolet (UV) B radiation and H₂O₂ on IL‐31 mRNA and protein expression in skin and different peripheral blood mononuclear cells (PBMCs). Methods The effects of UVB radiation and H₂O₂, as a prototypic reactive oxygen species, on IL‐31 mRNA and protein expression were analysed in various inflammation‐related cells and murine skin tissue. Results Treatment of cells with UVB radiation and H₂O₂ strongly induced IL‐31 mRNA and protein expression in human PBMCs and in the skin of SKH‐1 mice. Following exposure to UVB or H₂O₂, we observed increased expression of IL‐31 mRNA in T cells, monocytes, macrophages, and immature and especially mature dendritic cells. H₂O₂ treatment but not UVB radiation led to a moderate upregulation of IL‐31 mRNA expression in epidermal keratinocytes and dermal fibroblasts. Pretreatment of T lymphocytes with the MAPK p38 inhibitor SB203580 or the MEK1 inhibitor U0126 reduced the stimulatory effect of H₂O₂. These experiments suggest that p38 is involved in the regulation of IL‐31 expression in human skin. Conclusions Our studies reveal that UVB and reactive oxygen species stimulate the expression of IL‐31 in PBMCs and skin, especially in T cells, monocytes and monocyte‐derived dendritic cells.     

Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.     

Ultraviolet light treatment delays contact sensitization to nitrogen mustard

Contact sensitivity to nitrogen mustard was delayed after first treating patients with u.v. light. While the number of patients becoming sensitive to nitrogen mustard after ultraviolet light exposure was not significantly different from the control, the number of patients who became sensitive in the first 30 days was significantly less than the control group. It is postulated that this delay in sensitization is due to an alteration of the patients’ epidermal Langerhans cells, produced by the u.v. light exposure.     

Ultraviolet light exposure stimulates HMGB1 release by keratinocytes

The primary cause of non-melanoma skin cancer is ultraviolet (UV) light from the sun. Many studies have demonstrated that cutaneous inflammation resulting from UV exposure is important for the development of skin cancer. In fact, anti-inflammatory drugs have been shown to be effective in preventing skin cancer in animal models and in clinical trials. One new class of inflammatory mediators that could regulate UV-induced inflammation and skin carcinogenesis is alarmins. Alarmins are endogenous molecules that act as potent pro-inflammatory mediators when they are released by cells or accumulate extracellularly. The purpose of the current studies was to examine the expression and release of the alarmin high mobility group box 1 (HMGB1) after acute and chronic UV irradiation. Acute UV exposure stimulated the release of HMGB1 in cultured human keratinocytes and epidermal keratinocytes in murine skin. HMGB1 release correlated with pro-inflammatory cytokine production in vitro and inflammatory cell infiltration in vivo. HMGB1 was also examined in tumors arising in chronically irradiated murine skin. HMGB1 protein expression in low grade, benign papillomas was similar to adjacent skin. However, HMGB1 staining was more widespread with a higher number of HMGB1-positive cells observed in high grade papillomas and malignant tumors. Overall, the data suggest that HMGB1 may be an important regulator of UV-induced cutaneous inflammation and tumor formation. Additional studies are needed to assess whether targeting HMGB1 would be a useful strategy to prevent tumors from developing in response to chronic UV exposure.     

Ultraviolet light induces increased circulating interleukin-6 in humans

Although the clinical effects of acute exposure to ultraviolet (UV) light--such as cutaneous inflammation, malaise, somnolence, chills and fever--have been appreciated many years, the underlying mechanisms mediating these effects are poorly understood. Interleukin-6 (IL-6) is a potent cytokine with a wide variety of biologic activities, including induction of fever and acute phase response. Because IL-6 is produced by keratinocytes in vivo and in vitro and because the release is enhanced by UV light, the present study was performed to investigate the effect of a single UV dose eliciting moderate to severe sunburn reaction on the production of IL-6 in vivo. Therefore, plasma of UV-treated human subjects was evaluated for IL-6 activity by testing its capacity to induce the proliferation of an IL-6-dependent hybridoma cell line (B9). In contrast to plasma samples obtained before UV exposure, post-UV-specimens contained significant levels of IL-6 peaking at 12 h after UV irradiation. Plasma IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6, and upon HPLC gel filtration exhibited a molecular weight of around 20 kD. Moreover, plasma IL-6 levels correlated remarkably with fever course followed by an increase of acute phase proteins such as C-reactive protein. These data indicate that IL-6, which is released by keratinocytes following UV exposure, may gain access to the circulation and via its pyrogenic as well as acute phase-inducing effect may function as an important mediator of systemic sunburn reaction.     

Development and function of dendritic cells in health and disease.

The life history of dendritic cells (DC) is now established from their origins from bone marrow stem cells, their distribution through blood to the tissues, and their movement via afferent lymph to lymph nodes for the initiation of immune responses. Bone-marrow stem cells, and occasional stem cells in peripheral blood (about 1 per 10(5) mononuclear cells), can give rise both to DC and macrophages (MO). In addition to stem cells in blood, after short-term culture of mononuclear cells, three major morphologic types of DC can be separated (types I-III), which probably represent the maturational pathway of this cell type; type II cells resemble tissue DC such as Langerhans cells and type III have a veiled morphology similar to that seen in cells of afferent lymph and in the interdigitating cells of the paracortex of lymph nodes. Functionally, DC cultured from peripheral blood are able to acquire large antigens and process them like Langerhans cells of the skin. They can also present antigens to stimulate primary T-cell responses, a property associated with lymph node DC. In tissues, DC appear to act as outposts of the immune system, acquire antigens, and, particularly in primary responses, carry the antigens to lymph nodes where they initiate T-cell responses. In secondary responses, activation of memory T cells in the periphery and the acquisition of antigen/antibody complexes by follicular dendritic cells of the lymph node follicles, which stimulate B cell memory, may be more important pathways for immune activation. DC may play a role in the development of many immunologic diseases including cancer, autoimmunity, and acquired immunodeficiency syndrome (AIDS).