Gj Clydesdale

Ultraviolet light induced injury: Immunological and inflammatory effects

This article reviews many of the complex events that occur after cutaneous ultraviolet (UV) exposure. The inflammatory changes of acute exposure of the skin include erythema (sunburn), the production of inflammatory mediators, alteration of vascular responses and an inflammatory cell infiltrate. Damage to proteins and DNA accumulates within skin cells and characteristic morphological changes occur in keratinocytes and other skin cells. When a cell becomes damaged irreparably by UV exposure, cell death follows via apoptotic mechanisms. Alterations in cutaneous and systemic immunity occur as a result of the UV‐induced inflammation and damage, including changes in the production of cytokines by keratinocytes and other skin‐associated cells, alteration of adhesion molecule expression and the loss of APC function within the skin. These changes lead to the generation of suppressor T cells, the induction of antigen‐specific immunosuppression and a lowering of cell‐mediated immunity. These events impair the immune systems capacity to reject highly antigenic skin cancers. This review gives an overview of the acute inflammatory and immunological events associated with cutaneous UV exposure, which are important to consider before dealing with the complex interactions that occur with chronic UV exposure, leading to photocarcinogenesis.

Effects of UV on the migration and function of epidermal antigen presenting cells

Depletion of epidermal Langerhans cells (LC) and the concomitant depression of the skin immune system after excessive exposure to ultraviolet B light (UVB) has been established in the international literature for some time. Our investigations were intended to determine whether or not these phenomena occurred as a direct result of increased LC migration being triggered by the UVB exposure. To test this hypothesis, a sheep model was established in which the lymphatic vessels draining a defined region of skin were cannulated and the cells migrating towards the regional lymph node continuously collected. Cell populations in these collections were identified and enumerated by indirect immunofluorescence and flow cytometry. These experiments showed there was a significant, dose-dependent increase in the rate of LC migration from sheep skin after exposure to doses of UVB light exceeding 1 minimal erythemal dose (MED). In a series of parallel experiments, the functional characteristics of dendritic cells (DC) migrating from normal or UVB irradiated sheep were studied. To assay them, enriched preparations of DC were collected via cannulated afferent lymphatic vessels and pulsed with antigen prior to incubation with autologous peripheral blood lymphocytes. The relative efficiency of antigen presentation was determined by the ability of DC to induce T cell proliferation. Our data clearly demonstrate that there is a profound loss of normal antigen-presenting cell function after exposure to UVB light. Various experiments were undertaken to determine the mechanism(s) associated with these changes in migration kinetics and cellular function. Electron microscopic examinations of LC migrating from normal or UVB irradiated skin have demonstrated a profound loss of dendritic processes after UVB exposure. This provides a possible explanation for the changes in skin immunity after UVB exposure.

Migration of Langerhans cells and γδ + dendritic cells from UV-B-irradiated sheep skin

Depletion of dendritic cells from UV‐B‐irradiated sheep skin was investigated by monitoring migration of these cells towards regional lymph nodes. By creating and cannulating pseudoafferent lymphatic vessels draining a defined region of skin, migrating cells were collected and enumerated throughout the response to UV‐B irradiation. In the present study, the effects of exposing sheep flank skin to UV‐B radiation clearly demonstrated a dose‐dependent increase in the migration of Langerhans cells (LC) from the UV‐B‐exposed area to the draining lymph node. The range of UV‐B doses assessed in this study included 2.7 kJ/m2, a suberythemal dose; 8 kJ/m2, 1 minimal erythemal dose (MED); 20.1 kJ/m2; 40.2 kJ/m2; and 80.4 kJ/m2, 10 MED. The LC were the cells most sensitive to UV‐B treatment, with exposure to 8 kJ/m2 or greater reproducibly causing a significant increase in migration. Migration of γδ+ dendritic cells (γδ+ DC) from irradiated skin was also triggered by exposure to UV‐B radiation, but dose dependency was not evident within the range of UV‐B doses examined. This, in conjunction with the lack of any consistent correlation between either the timing or magnitude of migration peaks of these two cell types, suggests that different mechanisms govern the egress of LC and γδ+ DC from the skin. It is concluded that the depression of normal immune function in the skin after exposure to erythemal doses of UV‐B radiation is associated with changes in the migration patterns of epidermal dendritic cells to local lymph nodes.

Migration of Langerhans cells and gammadelta dendritic cells from UV-B-irradiated sheep skin.

Depletion of dendritic cells from UV‐B‐irradiated sheep skin was investigated by monitoring migration of these cells towards regional lymph nodes. By creating and cannulating pseudoafferent lymphatic vessels draining a defined region of skin, migrating cells were collected and enumerated throughout the response to UV‐B irradiation. In the present study, the effects of exposing sheep flank skin to UV‐B radiation clearly demonstrated a dose‐dependent increase in the migration of Langerhans cells (LC) from the UV‐B‐exposed area to the draining lymph node. The range of UV‐B doses assessed in this study included 2.7 kJ/m2, a suberythemal dose; 8 kJ/m2, 1 minimal erythemal dose (MED); 20.1 kJ/m2; 40.2 kJ/m2; and 80.4 kJ/m2, 10 MED. The LC were the cells most sensitive to UV‐B treatment, with exposure to 8 kJ/m2 or greater reproducibly causing a significant increase in migration. Migration of γδ+ dendritic cells (γδ+ DC) from irradiated skin was also triggered by exposure to UV‐B radiation, but dose dependency was not evident within the range of UV‐B doses examined. This, in conjunction with the lack of any consistent correlation between either the timing or magnitude of migration peaks of these two cell types, suggests that different mechanisms govern the egress of LC and γδ+ DC from the skin. It is concluded that the depression of normal immune function in the skin after exposure to erythemal doses of UV‐B radiation is associated with changes in the migration patterns of epidermal dendritic cells to local lymph nodes.

Migration of Langerhans cells and |[ggr]||[dgr]||[plus]| dendritic cells from UV-B-irradiated sheep skin

Depletion of dendritic cells from UV‐B‐irradiated sheep skin was investigated by monitoring migration of these cells towards regional lymph nodes. By creating and cannulating pseudoafferent lymphatic vessels draining a defined region of skin, migrating cells were collected and enumerated throughout the response to UV‐B irradiation. In the present study, the effects of exposing sheep flank skin to UV‐B radiation clearly demonstrated a dose‐dependent increase in the migration of Langerhans cells (LC) from the UV‐B‐exposed area to the draining lymph node. The range of UV‐B doses assessed in this study included 2.7 kJ/m2, a suberythemal dose; 8 kJ/m2, 1 minimal erythemal dose (MED); 20.1 kJ/m2; 40.2 kJ/m2; and 80.4 kJ/m2, 10 MED. The LC were the cells most sensitive to UV‐B treatment, with exposure to 8 kJ/m2 or greater reproducibly causing a significant increase in migration. Migration of γδ+ dendritic cells (γδ+ DC) from irradiated skin was also triggered by exposure to UV‐B radiation, but dose dependency was not evident within the range of UV‐B doses examined. This, in conjunction with the lack of any consistent correlation between either the timing or magnitude of migration peaks of these two cell types, suggests that different mechanisms govern the egress of LC and γδ+ DC from the skin. It is concluded that the depression of normal immune function in the skin after exposure to erythemal doses of UV‐B radiation is associated with changes in the migration patterns of epidermal dendritic cells to local lymph nodes.