Differential and Sequential Expression of Multiple Chemokines during Elicitation of Allergic Contact Hypersensitivity

Abstract

Regulation of chemokine-mediated leukocyte migration within inflammatory tissues is a complex event that cannot be mimicked and analyzed in vitro.Hapten-induced contact hypersensitivity (CHS) is a highly frequent, often occupationally related human skin disorder in industrialized countries with an enormous sociomedical impact. 1 Moreover, CHS is considered as a standard model for an antigen-specific, T-lymphocytemediated immune response. 2 This concept still holds true for the clinically nonapparent sensitization phase of CHS with antigen-processing and presentation by Langerhans cells and a consecutive T cell stimulation in the draining lymph node. However, there is increasing evidence that during the clinically visible and physically disturbing elicitation phase of CHS nonspecific hapten-induced proinflammatory effects precede or parallel the antigen-specific effect and are a conditio sine qua non for the vigorous inflammatory reactions. 2 In a mouse CHS model Grabbe and colleagues 3 demonstrated that nonspecific effects of epicutaneously applied haptens contribute to the elicitation of CHS. Proinflammatory irritative rather than antigen-specific properties of the hapten are furthermore responsible for the strict concentration-dependence of the effector phase of CHS. Therefore, it is tempting to speculate that such irritative properties of haptens promote inflammatory skin reactions via induction of proinflammatory cytokines, adhesion molecules, and chemoattractants. Accordingly, some contact allergens such as urushiol, the relevant hapten in poison ivy, and nickel sulfate have been demonstrated to directly induce inflammatory activation of keratinocytes resulting in expression of ICAM-1, interleukin (IL)-8, and/or tumor necrosis factor (TNF)-␣. 4 -6 In recent years, in particular chemokines have emerged as potent stimulators of effector cell accumulation and activation and are likely candidates to mediate leukocyte recruitment during elicitation of CHS. Since the description of IL-8 more than a decade ago, the supergene Supported by grants from the W. Sander-Stiftung (95.064.2) (to R. G.) and from the Deutsche Forschungsgemeinschaft (811/1-3) to M. G. M. G. and A. Trautmann contributed equally to this work.

Identification of Biologically Active Chemokine Isoforms from Ascitic Fluid and Elevated Levels of CCL18/Pulmonary and Activation-regulated Chemokine in Ovarian Carcinoma

“…Moreover, no homologue for human CCL18/PARC has been found yet in any other species. Human CCL18/PARC mRNA expression was observed in monocytic and dendritic cells (5, 20 -22), in normal lung, in hypersensitivity pneumonitis-affected lungs, in germinal centers of regional lymph nodes and tonsils, in atherosclerotic plaques, in inflamed liver, and in the dermis of contact hypersensitivity patients (5,20,(42)(43)(44)(45). However, little is known yet about the CCL18/PARC protein levels in vitro or in vivo.…”

A Second Step of Chemotaxis After Transendothelial Migration: Keratinocytes Undergoing Apoptosis Release IFN-γ-Inducible Protein 10, Monokine Induced by IFN-γ, and IFN-γ-Inducible α-Chemoattractant for T Cell Chemotaxis Toward Epidermis in Atopic Dermatitis

“…In allergic contact dermatitis, T lymphocytes transmigrate into the dermis driven by an early chemokine gradient. Chemokines, such as RANTES, MCP-1, thymus, and activation-regulated chemokine (CCL17), pulmonary and activation-regulated chemokine (CCL18), and macrophage-derived chemokine (CCL22) are reported to be involved in this process (41). In contrast to chemokines and adhesion molecules in T cell transendothelial migration, the chemokines IP-10, Mig, and iTac are expressed on late stages of contact dermatitis (41).…”

“…Chemokines, such as RANTES, MCP-1, thymus, and activation-regulated chemokine (CCL17), pulmonary and activation-regulated chemokine (CCL18), and macrophage-derived chemokine (CCL22) are reported to be involved in this process (41). In contrast to chemokines and adhesion molecules in T cell transendothelial migration, the chemokines IP-10, Mig, and iTac are expressed on late stages of contact dermatitis (41). In addition, IP-10 is up-regulated in the epidermis in inflammatory skin diseases like psoriasis or allergic contact dermatitis (42,43).…”

TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2

“…In situ hybridization experiments were performed as described previously 29 . Mouse cDNA probes were provided by J. M. Farber (Mig), T. A. Hamilton (IP-10), J.…”