Expression of CS-1 fibronectin precedes monocyte chemoattractant protein-1 production during elicitation of allergic contact dermatitis.

Abstract

Leucocyte migration within inflammatory skin compartments in allergic contact dermatitis (ACD) is the result of a sophisticated multi-step event where multiple molecules are involved. Since non-antigen-specific mechanisms have been described as an early participant in elicitation of ACD, we investigated the kinetics of the expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and the type of infiltrating cells. We compared the time course production of MCP-1/CCL2 with connecting segment-1 (CS-1) fibronectin and thymus and activation-regulated chemokine (TARC/ CCL17) expression. Biopsies from 10 individuals challenged in their back with the antigen responsible for their contact dermatitis and an irrelevant antigen were taken at different times and histology, immunohistochemistry for CS-1 fibronectin, TARC/CCL17, CD3, CD68, CXCR3, CCR4 and in situ hybridization for MCP-1/CCL2 were performed. At positive antigen stimulated sites expression of MCP-1/CCL2 by basal keratinocytes and isolated cells in dermis started at 10 h. CS-1 fibronectin and TARC/CCL17 expression by blood endothelial cells was found at 2 and 10 h, respectively. This was followed by dermal accumulation of mononuclear cells with a significant increase of CD3+ and CD68+cells. At 48 h, approximately 58% of infiltrating cells were CXCR3+, and 35% CCR4+. We showed evidence of the fact that CS-1 fibronectin expression precedes the production of MCP-1/CCL2 and TARC/CCL17 in the skin of patients with ACD, suggesting that these molecules participate in the early complex process of migrating mononuclear cells during elicitation of ACD.