Effect of complement and polymorphonuclear leukocyte depletion on experimental skin lesions resembling systemic lupus erythematosus

Abstract

Immunopathologic cutaneous lesions resembling human systemic lupus erythematosus (SLE) can be induced in mice sensitized to ultraviolet (UV)-irradiated DNA following whole body irradiation with UV light. The lesions are characterized by the formation of immune complexes at different skin sites. The role played by cellular and humoral mediators in the pathogenesis of this experimental model was investigated. The results obtained suggest that inflammation that follows UV radiation is the major factor responsible for this pathology. Accordingly mice that were rendered neutrophil (PMN) deficient did not manifest skin lesions, and depletion of C3 complement component left them unchanged. I n addition time course studies showed that PMN depletion did not prevent a delayed skin involvement. Thus multiple factors seem to mediate the onset of the immunopathologic changes previously described. chemically altered DNA molecules are able to induce a specific immune response (1,2).Native DNA irradiated with ultraviolet (UV) light (UV-DNA) is highly immunogenic (3) and has been used in experimental animal models to elucidate some of the immunologic events leading to kidney (4) and skin (5) involvement in systemic lupus erythematows in humans. Cutaneous lesions in particular could be induced with high frequency in mice with circulating antibodies to UV-DNA following exposure to UV light. This treatment has been shown to be capable of inducing formation of the UV-DNA photoproduct, thymidine dimer (6), and of releasing it from the skin into the blood stream (7).The skin immunopathology closely resembled human lesions in that in vivo fixation of mouse 7-globulins and C3 complement component to epidermal cell nuclei and dermal-epidermal junction could be observed together with accumulation of inflammatory cells. In order to investigate the role played by cellular and humoral mediators in the formation of these lesions, the effect of polymorpholeukocyte (PMN) and complement (C3) depletion on the appearance of skin immunopathology was investigated. Results of experiments reported here showed that PMN accumulation in the skin, which follows UV light irradiation, is indispensable for the onset of the cutaneous pathology. C3 depletion prevented only in vivo binding of the complement component to the skin sites where mouse y-globulins were bound to UV-DNA antigen.

Ultraviolet Radiation on Innate Immunity and Growth of Broad‐Snouted Caiman (Caiman latirostris): Implications for Facilities Design

“…We suspect that the reduction in serum complement system activity at 8 and 16 hr per day of artificial UV/visible light demonstrates a UVA‐B dose‐dependent response, which might affect the IS of captive herpetofauna. Similar reports were obtained in mice using experimental skin lesions, in which long UVR is the major factor responsible for this pathology [Natali et al, ]. Up to now, the details of how UV exposure may suppress the immune responses have not been elucidated.…”

Neutrophil extracellular traps drive lupus flares with acute skin and kidney inflammation triggered by ultraviolet irradiation

“…A recent study using a single high dose of UVB irradiation on WT mice revealed transient proteinuria, accompanied by the transmigration of neutrophils from the inflamed skin to the kidneys, as monitored by a photoactivatable lineage tracking approach ( 31 ), highlighting the potential dermal-renal crosstalk in response to the acute skin injury. In addition, a previous study demonstrated that neutrophil depletion protects mice from developing UV-irradiation-induced lupus-like skin lesions ( 42 ). On the other hand, skin infection by staphylococcal aureus in Nfkbiz ΔK5 mice promotes keratinocyte apoptosis, neutrophil activation and NET release, leading to SLE-like autoimmune inflammation and kidney injury ( 32 ).…”