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Vol. 52, Issue 1, 145-176, March 2000
Laboratory of Host Defenses, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland
(P.M.M.); Theodor-Kocher Institute, Bern, Switzerland (M.B.); Gladstone
Institute of Cardiovascular Disease, San Francisco, California
(I.F.C.); Genentech, Inc., South San Francisco, California (C.A.H.);
Department of Immunology, Berlex Biosciences, Richmond, California
(R.H.); Department of Molecular Preventive Medicine, School of
Medicine, University of Tokyo, Bunkyoku, Tokyo, Japan (K.M.);
Laboratory of Parasitic Diseases, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland
(L.H.M.); Laboratory of Molecular Immunoregulation, Division of Basic
Science, National Cancer Institute-Frederick Cancer Research and
Development Center, Frederick, Maryland (J.J.O.); and Serono
Pharmaceutical Research Institute, Plan-les-Ouates, Geneva, Switzerland
(C.A.P.)
I. Overview
II. Introduction
A. Historical Background
B. Chemokine Classification
C. Chemokine Receptor Classification and Nomenclature
D. Chemokine Receptor Structure
E. Chemokine Receptor Specificity for Ligands and Leukocytes
III. CXC Chemokine Receptor Subtypes
A. CXCR1 and CXCR2
B. CXCR3
C. CXCR4
D. CXCR5
IV. CC Chemokine Receptor Subtypes
A. CCR1
B. CCR2
C. CCR3
D. CCR4
E. CCR5
F. CCR6
G. CCR7
H. CCR8
I. CCR9
J. CCR10
K. CCR11
V. CX3C Chemokine Receptor Subtypes
A. CX3CR1
VI. Chemokine Receptor Subtypes
A. XCR1
VII. Chemokine Binding Proteins
A. Duffy
B. D6
VIII. Virus-Encoded Chemokine Receptors
A. ECRF3
B. US28
C. KSHV GPCR
D. UL12
E. E1
IX. Conclusions
Acknowledgments
References
Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area.
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