The Chemokine Factsbook: Ligands and Receptors

By Krishna Vaddi, Margaret Keller and Matthew Newton

How do you keep track of basic information on the proteins you work with? Where do you find details of their physicochemical properties, amino acid sequences, gene organization? Are you tired of scanning review articles, primary papers and databases to locate that elusive fact?

The Academic Press FactsBook series will satisfy scientists and clinical researchers suffering from information overload. Each volume provides a catalog of the essential properties of families of molecules. Gene organization, amino acid sequences, physicochemical properties, and biological activity are presented using a common, easy-to-follow format. Taken together they compile everything you want to know about proteins but are too busy to look for. The Chemokine FactsBook contains more than 40 entries on chemokines, and chemokine receptors from human or other origin, including IL-8, MCP-1, C5-a, RANTES, Lymphotactin, and CC CKR-1.

The text provides information on tissue sources, target cells, physicochemical properties, transcription factors, regulation of expression in disease, receptor-binding characteristics, gene structure and location, amino acid sequences, and accession numbers and references.

• Contains over 40 entries on chemokines and chemokine receptors from human or other origin, including:
• IL-8
• MCP-1
• C5-a
• RANTES
• Lymphotactin
• CC CKR-1
• Entries provide information on:
• Tissue sources
• Target cells
• Physicochemical properties
• Transcription factors
• Regulation of expression
• Expression in disease
• Receptor-binding characteristics
• Gene structure and location
• Amino acid sequences
• Database accession numbers
• References

• Language: English
• Publisher: Academic Press
• Release date: Apr 1, 1997
• ISBN: 9780080529080

Book preview

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Introduction

AIM OF THE BOOK

The primary goal of this book is to provide researchers with a source of comprehensive information on the rapidly evolving family of intercellular mediators known as ‘chemokines’. As new proteins of biological importance are being identified almost every day, it is nearly impossible to keep up with their functions and other facts that make them useful tools in our daily research. These proteins are exquisitely specific in their effects on cell types and the responses they elicit. We often find ourselves digging through the literature to find what they do, how they are regulated and how they could be mediating the effects we find in our own research. The authors of the previously published Cytokine FactsBook did a phenomenal job of putting together most of the facts on cytokines and included extensive information on chemokines as well. We have tried to make the present book complementary to the Cytokine FactsBook by providing more detailed information on the biological effects, regulation of expression, expression in different disease states (both human diseases and animal models), in addition to the basic facts that readers have come to expect from a book in this series.

HOW DO CHEMOKINES DIFFER FROM CYTOKINES?

Although still considered as members of the cytokine superfamily, chemokines are rapidly establishing their own identity as a class of molecules with very distinct effects. The name chemokine comes from a combination of chemotactic and cytokines and chemotaxis or signaling for directed migration has been the central concept, besides the structural similarities, that distinguishes this class of proteins as a family. It is clearly established that many pathological as well as physiological processes are closely regulated by a given cell type, and scientists have long wondered about the signals that could specifically draw a given cell into a given tissue. As Schall aptly put it ‘Like the physicists’ dark matter, the existence of chemokines had been long suspected, but their nature in the immunological cosmos was undefined until recently’¹.

With the identification of IL-8, which is chemotactic to granulocytes but not monocytes, it appeared clearly possible to have a protein that could specifically deliver a migratory signal to a specific cell type. This finding was in sharp contrast to those that show lack of cell specificity such as formyl peptides, C5a, and LTB4. Discovery of MCP-1 represents another important milestone in the evolution of the chemokine family. MCP-1 is primarily chemotactic to mononuclear leukocytes but not polymorphs, and hence seen to play an important role in chronic inflammatory diseases. Identification of IL-8 and MCP-1 marks a new era in chemotaxis biology, and serious efforts have begun to explore other proteins such as those that could be chemotactic to other cell types.

Another important turning point for the chemokine field came about with the identification of heptahelical receptors for IL-8. Subsequently several chemokine receptors have been identified, and as far as we know today, chemokines are the only members of the cytokine superfamily that bind to receptors that are seven-transmembrane and G-protein coupled in nature; another feature that makes the chemokines distinct. These findings also opened up a whole new area of research exploring new chemokine receptors and how each of the chemokines interacts with their receptors. Intense research is currently focused on understanding the specificity of chemokines and their receptors utilizing structural and functional studies with the goal of identifying of molecules that could specifically modulate receptor–ligand interactions.

However, as of today, we are not really sure if the most important physiological function of chemokines is chemotaxis alone. Recent findings² on the molecular basis of the angiogenic and the angiostatic effects of chemokines have sparked a great interest in their role in physiological and pathological conditions that require neovascularization. Even more recently, the discovery of a relationship between β-chemokines and the resistance to human immunodeficiency virus infection³ has created newer avenues of scientific exploration of the real biological role of chemokines. Other novel biological effects of chemokines such as T-cell costimulatory effects are also beginning to