ReviewChemokines in allergy
Introduction
During recent years the prevalence of atopic and allergic diseases has increased rapidly in developed countries. These diseases represent complex and chronic inflammatory disorders that involve the recruitment and activation of many inflammatory and structural cells, all of which release inflammatory mediators that result in the typical pathophysiological changes observed in the airways or skin. Along with adhesion molecules, chemokines and their receptors are believed to be essential for leukocyte trafficking from the circulation into inflammatory tissues. This report represents a brief summary of the association of chemokines and their receptors with atopic diseases such as asthma and atopic dermatitis. Based on these data, we propose two models for the potential roles of chemokines and their receptors in these diseases (depicted in Figure 1, Figure 2).
Section snippets
The chemokine and chemokine receptor superfamily: current status
Chemokines are small, secreted proteins that regulate leukocyte trafficking. Recently, knowledge of this superfamily has grown significantly due to the availability of large databases of expressed sequence tags (ESTs) and bioinformatics [1••]. In fact the chemokines are probably the best example of the impact of these new gene-discovery methods, since their structural features make it easy to recognize new members in EST databases. These chemoattractants share structural similarities, including
Chemokine receptors and Th1 and Th2 cells
Th2 cells have been shown to play an important role in atopy and allergic diseases. In contrast, delayed-type hypersensitivity reactions — such as contact allergic responses — are believed to be mediated by Th1 cells.
Recently, several groups investigated the chemokine receptors expressed by Th1 cells compared with Th2 cells. Sallusto et al. [2] showed that human IL-4-producing cells express CCR3, suggesting that Th2 cells express this marker. Using northern blot analysis, Bonecchi et al. [3•]
Chemokines and their receptors in the pathogenesis of atopic asthma
Asthma represents a chronic inflammatory lung disease with T-cell-mediated inflammation of the bronchial mucosa characterized by an influx of eosinophils [9]. Eosinophils are thought to be the primary cells responsible for the induction of bronchial mucosal injury and are associated with bronchial obstruction during asthmatic responses 10, 11. In atopic (‘allergic’) asthma, production of Th2 cytokines — such as IL-4 and IL-5 — correlates with disease severity and eosinophil infiltration 9, 12,
Chemokines and their receptors in the pathogenesis of atopic dermatitis
Atopic dermatitis represents one of the most common skin diseases, with a lifetime prevalence of up to 20% 44, 45 and an increasing number of cases 46, 47, 48. Clinically this chronic or chronically relapsing inflammatory skin disease is characterized by eczematous lesions with typical morphology and distribution, severe pruritus, elevated serum IgE, the presence of allergen-specific IgE and peripheral blood eosinophilia [49]. Histopathologically, the lesional skin of atopic dermatitis patients
Conclusions
What we can learn from studying chemokines and chemokine receptors in the complex immunopathogenesis of atopic diseases is that these mediators most probably work in an interdependent fashion and their sequential (orchestrated) production will contribute to inflammatory processes that develop into the disease phenotype. Future studies will address questions about the chemokine receptors responsible for Th2 cell recruitment in vivo, whether viral chemokines contribute to disease
Acknowledgements
DNAX Research Institute is supported by the Schering-Plough Corporation (Madison, New Jersey). We thank Edith Hessel and Luis Teran for comments and Maribel Andonian for her help with the illustrations. We thank O Yoshie for proposing the new chemokine nomenclature.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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