Chemokines and their receptors in allergic disease

Abstract

Mechanisms of chemoattraction underlie the spatial organization of the cells of the immune system under basal conditions and the localization of these cells to sites of inflammation. The chemokines, a family of around 50 small proteins, play a major role in these processes. Leukocytes are equipped with cell-surface sensors for chemokines. There are 19 such receptors that are differentially expressed on leukocytes: the repertoire of receptor expression depending on the type of leukocyte and its stage in maturation. From observations in animal models, clinical studies, in vitro cell biology, and molecular analysis, a working hypothesis has been established to explain the cellular interactions underlying allergic responses and the chemokines-chemokine receptors involved. Chemokines signal through G protein-coupled receptors that are used typically for sensory functions (eg, detection of olfactory signals in the nose). This type of receptor can be blocked selectively by small-molecule antagonists. This provides the opportunity for the development of therapeutic compounds designed to suppress the recruitment of particular leukocyte types in allergic reactions.