No abstract

The immune response to an allergen is not only dependent on the inflammatory stimulus, but also on the genetic disposition of the individual. Important effector cells in the immune response are myelomonocytic cells in their various differentiation stages. We recently described the expression of MRP8 and MRP14, two calcium-binding proteins of the S-100 family, by these cells during inflammatory activation. Here, we investigated whether their expression in murine contact dermatitis is dependent on the stimulus by which dermatitis is elicited, and if it is related to the genetic constitution of different inbred strains of mice. Therefore we performed immunohistochemical studies on the distribution of MRP8- and MRP14-positive cells during experimentally induced allergic (ACD) and irritant contact dermatitis (ICD). Both forms of dermatitis were elicited in BALB/c and C57B1/6 mice. BALB/c mice were found to react with a more intense inflammatory response in both ACD and ICD (high responders) than C57B1/6 mice (low responders). The expression of MRP8 and MRP14 in both forms of dermatitis correlated with the early influx of macrophages and with the cell density of the infiltrate. Also the percentage of MRP8-and MRP14-positive cells in the infiltrate during ACD or ICD was higher in the more intense inflammatory reaction of BALB/c mice compared to C57B1/6 mice. We conclude that MRP8 and MRP14 define a differentiation stage of inflammatory macrophages and that their expression correlates with the activity of inflammatory processes.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the interaction of immunocompetent cells in inflammation. It contributes to lymphocyte recruitment, antigen presentation and T-cell activation. Recently, the murine homologue of ICAM-1, originally designated as MALA-2, has been identified. The monoclonal antibody YN1/1.7 for murine ICAM-1 enables the analysis of ICAM-1 expression in murine allergic contact dermatitis, a prototype of cutaneous T-cell-mediated inflammatory response. At 0, 1, 8, 24, 48, 72 h, and 7 and 14 days after challenge with 2,4-dinitrofluoro-1-benzene (DNFB) cryostat sections of ear skin were immunostained for ICAM-1, I-A and mononuclear cells (L3T4, Lyt-2, BM8). In normal skin ICAM-1 labeling was restricted to endothelial cells and dermal dendritic cells/macrophages; keratinocytes (KCs) did not express ICAM-1. The dermal cellular infiltrate increased progressively from 8 to 72 h after DNFB challenge. The majority of infiltrating cells were BM8+ macrophages (75%) and L3T4+ (10%) or Lyt-2 + T cells (10%); maximally 30% of those stained positive for ICAM-1. At 24 h, focal ICAM-1 expression on KCs developed, reached a maximum at 72 h and faded therafter. Migration of T cells into the epidermal layer started at 48 h at sites which had already expressed ICAM-1. Our data provide evidence that expression of ICAM-1 by epidermal cells precedes infiltration of the epidermis by T lymphocytes as shown before in human cutaneous disorders. Thus, a mouse model may be useful to investigate the role of ICAM-1 in inflammation further.

Two strains of mice, BALB/c and C57B1/6, which are known to differ in their inflammatory responsiveness to allergens, were analyzed regarding their expression of macrophage migration inhibitory factor (MIF). Allergic contact dermatitis to 2,4-dinitro-1-fluorobenzene and irritant contact dermatitis to croton oil were studied immunohistologically at designated time intervals after elicitation. BALB/c mice presented a significantly more intense ear swelling response than C57B1/6 mice and showed a strong endothelial MIF expression in the early phase of inflammation in both allergic and irritant contact dermatitis. Endothelial MIF expression was much weaker in C57B1/6 mice. Furthermore, the infiltration rate of inflammatory cells (MIF+ and BM8+ macrophages, Lyt2+ and L3T4+ T cells) was significantly higher in BALB/c than in C57B1/6 mice. We conclude that genetically determined differences of susceptibility to allergens and irritants in BALB/c and C57B1/6 mice are reflected by the intensity of MIF expression in the microvascular endothelium and immigrating inflammatory cells. MIF seems to appear as first molecular equivalent of developing inflammation and probably determines the degree of cellular infiltration.