Chemokines: A New Classification System and Their Role in Immunity

Chemokines are a group of small ( similar to 8-14 kDa), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of seven-transmembrane, G protein-coupled receptors. About 40 chemokines have now been identified in humans. They mainly act on neutrophils, monocytes, lymphocytes, and eosinophils and play a pivotal role in host defense mechanisms. The study of chemokines has recently overlapped more with other fields of immunology. It has now become evident that chemokines play fundamental roles in the development, homeostasis, and function of the immune system. The rapid increase in the number of chemokines along with other complex issues described below have led to a situation where a newcomer attempting to understand this field faces a daunting task. In this review, our goal is to present a concise overview of the chemokine super-family. The chemokines have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system (Ma et al., 1998) or endothelial cells, where they result in either angiogenic or angiostatic effects (Strieter et al., 1995). However, the scope of this review makes it difficult to provide a comprehensive view of such a complex and expanding field. For this reason, we will focus on several areas of chemokine biology of particular interest to immunologists. The development of EST (expressed sequence tag) databases and bioinformatics (computer-assisted sequence analysis) have allowed the rapid identification of novel genes. The chemokines have been particularly well suited for these techniques since they represent very abundant messages in those cells that express them. Since they are small proteins, the probability that their entire coding regions were represented as ESTs in databases was very high. As a result, the chemokines have been one of the first molecular families to experience the full impact of genomics and bioinformatics, to the point that it is very likely that most of them have now been discovered. This allows us to take a global perspective of the field for useful lessons that we may be able to apply to other molecular families in the future.