Review
A closer look at chemokines and their role in asthmatic responses

https://doi.org/10.1016/j.ejphar.2005.12.064Get rights and content

Abstract

Inflammatory cell recruitment is a hallmark phenomenon of all inflammatory diseases, including allergic asthma. In allergy and asthma, recruitment of inflammatory cells such as T cells, dendritic cells, mast cells, eosinophils and neutrophils, is mediated via a number of chemokines and their receptors. Not only are chemokines involved in recruitment of these cells, they also play a role in activation and differentiation of inflammatory cells, among others, by selectively activating Th1 or Th2 cells or by effects on epithelial or endothelial cells. Binding of chemokines with their receptors has been demonstrated to be highly promiscuous and the subsequent activation pattern on effector cells is very heterogeneous, which has lead to confusion and has complicated research in this field. Nonetheless, chemokines and their receptors are important potential therapeutical targets in allergy and asthma because of their central role in cell recruitment and activation during inflammation.

Section snippets

Asthma

The word “asthma”, which literally means panting, was already employed by Greek physicians of antiquity such as Hippocrates. Aretaeus of Cappadocia in the second century AD gave the first accurate clinical description of asthma: “the symptoms of its approach are heaviness of the chest; sluggishness to one's accustomed work, and to every other exertion; difficulty of breathing in running on a steep road”, and acknowledged that the disease was potentially fatal. It was not before 1910 that

Chemokines and their receptors

Chemokines represent a large family of proteins secreted by many immune and non-immune cells with an essential role in inflammatory and immune reactions. Chemokines have been divided in four main groups based on their molecular structure and the position of two cysteine residues: CC and CXC (alpha), and the less described C and CX3C families. So far, 28 CC (CCL), 16 CXC (CXCL), 2C (CL) and 1 CX3C (CX3CL) chemokine ligands have been identified (Table 1). All groups of chemokines bind to their

Animal models for allergic asthma

Experimental support for the role of several immunological mechanisms in allergic diseases is largely derived from animal models for asthma. Although rat and guinea pig models are relevant, the mouse model is most used, due to the superior availability of immunological tools, such as congenic, transgenic and knock out mouse strains, antibodies and recombinant protein mediators. Although the mouse model does not replicate human disease perfectly, much of what is known about the immunobiology of

Chemokine targets in asthma

Although the chemokine system initially seemed an excellent target for treatment of diverse inflammatory diseases, recently it is realized that targeting chemokines is not as straight forward. The main problems with targeting the chemokine system for treatment have been the large number of different chemokines (about 50) that are upregulated during inflammation, the overlap in chemokine function and the pleiotrophy of chemokine–receptor interaction. In addition, treatment of asthma by targeting

Conclusions

Without a doubt, chemokines play an important role in the establishment and persistence of allergic asthma. In this multifactorial disease, chemokines and their receptors are involved at multiple levels in different stages of disease (Fig. 2). Classically, chemokines were thought to be involved in the recruitment of leukocytes. Recently however, research suggests that chemokines can also influence the immune response by activation and differentiating different cell populations involved in

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