Structure and Function of Leukocyte Chemoattractant Receptors

Abstract

Publisher Summary Leukocytes are capable of migrating along a chemical gradient, a phenomenon known as chemotaxis. The accumulation of phagocytic leukocytes (phagocytes) at sites of inflammation is of particular importance for host defense against invading microorganisms and for wound healing. Migration of lymphocytes is believed to be essential for T-cell development and maturation. In several pathological conditions, the local accumulation of phagocytes and the subsequent release of superoxide anions and proteolytic enzymes are responsible for tissue damage associated with inflammatory disorders. The broad application of molecular cloning techniques has led to the delineation of the primary structures of many chemoattractant receptors. These leukocyte chemoattractant receptors share significant sequence homology and structural features, and together they constitute a subfamily within the G protein-coupled receptor (GPCR) superfamily. This chapter is intended to briefly summarize the current understanding of the structure and function of G protein-coupled leukocyte chemoattractant receptors. These receptors represent specific cell surface binding sites for the classical chemoattractants (N-formyl peptides, C5a, PAF, LTB4), and the α, β chemokines. The chapter discusses the chemoattractant-induced leukocyte function. There is molecular characterization of the structure of chemoattractant receptors: their biochemical characterization and molecular cloning—receptors for classical chemoattractants and chemokine receptors—and the receptor structure. There are pharmacological and biochemical properties of chemoattractant receptors—ligand-receptor interactions, coupling of G proteins to chemoattractant receptors, phosphorylation and desensitization of chemoattractant receptors—chemoattractant receptor homologs, and potential therapeutic interventions for chemoattractant receptor activation. Recent advances in the molecular cloning of chemoattractant receptors have generated enormous amounts of information regarding the structure-function relationships of these receptors. It is now clear that chemoattractant receptors, as a subgroup of the GPCR superfamily, have their own unique pharmacological and biochemical properties. Understanding of the signaling mechanisms is essential to the development of new strategies for the control of inflammatory cell activation.