Expression of Monocyte Chemoattractant Protein-1 in Basal Keratinocytes of Psoriatic Lesions

Abstract

To further our understanding of psoriasis (PS) pathogenesis, it is necessary to analyze the factors responsible for the abnormal cutaneous topobiology of infiltrating leukocytes, in particular the juxtaposition of proliferating basal keratinocytes (KC) to immunocompetent cells. Surprisingly, our immunohistological analysis of psoriatic lesions (n = 11) revealed that, as opposed to neutrophils and T cells, basically mobile dermal macrophages/dendrocytes (DM/DD) are almost exclusively restricted to the dermal compartment with only few cells penetrating the basal membrane. They are encountered in the papillary dermis and are frequently arranged along the basement membrane of the cubbing rete ridges, thus having the closest spatial proximity to proliferating KC. Recently, the potent monocyte chemoattractant protein-1 (MCP-1) was isolated and sequenced. Since T cells, fibroblasts, endothelial cells, smooth muscle cells and KC have the potential to secrete MCP-1 in vitro and all cell types are integral parts in lesions of PS, we performed in situ hybridization studies with ³⁵S-labelled MCP-1 RNA probes to detect and localize MCP-1 mRNA expression. Using MCP-1 antisense but not sense probes, we consistently detected highly abundant silver grain precipitates along the basal epidermal layer of the tips of the rete ridges and to a lesser extent in cells residing in the papillary dermis. In contrast, all suprabasal epidermal cells and (except few single cells) the resident and passenger cells in the dermal compartment were quiescent. Thus, the highest concentration of MCP-1 is most likely achieved at the dermal-epidermal junction and may explain the particular distribution of DM/DD in PS. This suggests that a dialogue between proliferating KC and DM/DD, mediated by MCP-1, is one of the dominating regulatory events in PS pathogenesis.