We investigated the expression of C5a receptor (C5aR) and the subfamily receptor, C5L2, in human in flammatory skin diseases. C5L2 is known to be the decoy protein for C5aR. Neutrophils and monocytes infiltrating the inflammatory skin lesions were positively stained with anti-C5aR and anti-C5L2 anti bodies. In particular, the infiltration of myeloperoxidase (MPO)-positive neutrophils around the small vessels of the dermis or subcutis of either anaphylactoid purpura or erythema nodosum was remarkable. In psoriasis vulgaris, both MPO-positive and CD68-positive cells were detected around Munro’s microabscess, but were only sparsely positive in the papillary layer of the dermis similarly, in atopic dermatitis, the positivity with the antibodies in the dermis was not remarkable. Both C5aR and C5L2 co-expressed on MPO- and/or CD68-positive cells, as detected by the immunofluorescent multiple staining. Although many of the MPO- and CD68-positive cells had not infiltrated into the upper dermis of either psoriasis vulgaris or atopic dermatitis, expression of the mRNAs of C5aR, C5L2 and C3aR, both in the granulocyte fractions and the monocyte fractions of the whole peripheral blood of these skin diseases, was increased with statistical significance as compared to that in the fractions of normal volunteers. Thus, it is concluded that an increase in the expression of C5aR on the surface of MPO-positive and CD68-positive cells also induces the concomitant expression of C5L2, and that activated granular leucocytes and monocytes in the peripheral blood extravasate and migrate into the target lesions locally in re sponse to the concentrations of C5a and/or C5a-des-Arg in the skin. The mechanism and significance of the expression of C5L2 in neutrophilic inflammatory skin diseases should be further investigated.
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