The Chemokine Receptors (eBook)

Preface 6
Contents 7
Contributors 9
Color Plate 13
1 The Birth and Maturation of Chemokines and Their Receptors (Nicholas W. Lukacs and Jeffrey K. Harrison) 14
1.1. Birth of Chemotactic Cytokines, or Chemokines 14
1.2. Identification of Chemokine Receptors as G Protein – Coupled Receptors 17
1.3. Chemokine Receptors: Beyond Migration of Leukocytes 18
1.4. The Future of Chemokine Receptors: Are They Valid Drug Targets? 19
References 20
2 The Structural Biology of Chemokines (Elias Lolis and James W. Murphy) 22
2.1. Introduction 22
2.2. Chemokine Structures 24
2.3. Chemokine-Receptor Interactions 33
2.4. Chemokine-Glycosaminoglycan Interactions 36
2.5. Future Directions 38
References 38
3 Chemokine Receptors: A Structural Overview (Gerard J. Graham and Robert J. Nibbs) 44
3.1. Background of the Chemokine Receptors 44
3.2. Ligand Binding by Chemokine Receptors 47
3.3. Primary Structural Determinants of Chemokine Receptor Function 50
3.4. Signaling by Chemokine Receptors 56
3.5. Chemokine Receptor Dimerization 57
3.6. Determination of the Three-Dimensional Structure of the Chemokine Receptors 59
3.7. Conclusions 61
References 61
4 Chemokine Signaling in T- Lymphocyte Migration: The Role of Phosphoinositide 3- kinase (Laura Smith, Adam Webb, and Stephen G. Ward) 68
4.1. Introduction 69
4.2. The Role of Phosphoinositide 3-kinase(s) in T- Lymphocyte Migration 69
4.3. What Is the Signi.cance of Rho GTPases in T- Lymphocyte Migration? 75
4.4. Activation of Protein Tyrosine Kinases by Chemokines: Relevance to T- Lymphocyte Migration 76
4.5. Evidence of a Role for Protein Kinase C Activation in T- Lymphocyte Migration 77
4.6. Importance of Tailoring the Migratory Response 78
4.7. Conclusions 80
References 80
5 Chemokine Receptors and Neutrophil Trafficking (Teizo Yoshimura) 84
5.1. Introduction 84
5.2. Role for CXCR1 and CXCR2 in Tissue In.ltration of Neutrophils 85
5.3. Role for CC Chemokine Receptors in the Traf.cking of Neutrophils 88
5.4. Role for CXCR4 in Neutrophil Retention and Mobilization 91
5.5. Conclusions 93
Acknowledgments 94
References 94
6 Chemokine Receptors and Dendritic Cell Trafficking (Hiroyuki Yoneyama, Kenjiro Matsuno, and Kouji Matsushima) 100
6.1. The Concept of Migration-Dependent Dendritic Cell Activation 100
6.2. Two Subsets of Naïve Dendritic Cells with Distinct Migration and Functional Potentials 102
6.3. The Impact of Migration of Dendritic Cells on Their Effector Functions 105
6.4. Regulation by Chemokines of Dendritic Cell Migration– Dependent Immunity 107
6.5. Induction of Primed pDCs by Trans-HEV Migration 108
6.6. Concerted Recruitment of mDCs and pDCs: The Role of Chemokines 109
References 111
7 Chemokine Receptors and Lymphocyte Trafficking (Michael N. Hedrick and Joshua M. Farber) 113
7.1. Chemokines and Primary Lymphoid Organs 114
7.2. Chemokines and Secondary Lymphoid Organs 116
7.3. Chemokines and Lymphocytes in the Periphery 117
7.4. Conclusions 123
References 123
8 Chemokines in Trafficking of Hematopoietic Stem and Progenitor Cells and Hematopoiesis (Chang H. Kim) 131
8.1. Introduction 132
8.2. Regulation of Survival and Proliferation of Hematopoietic Stem and Progenitor Cells by Chemokines 133
8.3. Regulation of the Homing and Mobilization of Hematopoietic Stem and Progenitor Cells 136
8.4. Development of Hematopoietic Cell Lineage–Specific Migration Program 139
8.5. Conclusions 142
Acknowledgments 143
References 143
9 Chemokines in Transplantation Biology (Peter Jon Nelson, Stephan Segerer, and Detlef Schlondorff) 151
9.1. Introduction 151
9.2. The Immunobiology of Vascularized Allografts 152
9.3. Chemokines and the Directed Recruitment of Leukocytes into Allografts 154
9.4. Chemokine Polymorphisms as Predisposing or Prognostic Factors 161
9.5. Conclusions 161
References 161
10 The Chemokine System and Arthritis (Marlon P. Quinones, Fabio Jimenez, Carlos A. Estrada, Hernan G. Martiniez, and Seema S. Ahuja) 167
10.1. Introduction 167
10.2. Role of Chemokines During the Different Phases of Rheumatoid Arthritis 168
10.3. Effects of Chemokine System Inactivation in Arthritis 182
10.4. Signaling Cascades Underlying the Effects of Chemokines in Arthritis 191
10.5. Some Unsolved Issues Regarding Chemokines in Arthritis 191
10.6. Effects of Chemokines in Rheumatoid Arthritis Beyond Cell Recruitment 194
10.7. Conclusions 196
Acknowledgments 196
References 196
11 Chemokine Receptors in Atherosclerosis (Maya R. Jerath, Mildred Kwan, Peng Liu, and Dhavalkumar D. Patel) 211
11.1. Introduction 211
11.2. Animal Models 218
11.3. Chemokines and Receptors 219
11.4. Therapeutic Implications 230
11.5. Conclusions 233
References 234
12 Chemokine Receptors in Allergic Lung Disease (Dennis M. Lindell and Nicholas W. Lukacs) 246
12.1. Introduction 247
12.2. Th1 versus Th2 Chemokine Receptor Pro.les 248
12.3. CCR3 253
12.4. CCR1 255
12.5. CCR2 255
12.6. CXCR4 257
12.7. CXCR1/CXCR2 257
12.8. CX3CR1/CX3CL1 258
12.9. Conclusions 258
Acknowledgments 260
References 260
13 Chemokine Receptors and HIV/AIDS (Tzanko S. Stantchev and Christopher C. Broder) 269
13.1. Introduction 269
13.2. HIV-1 Tropism 271
13.3. Transmission of HIV-1 Infection 272
13.4. Exploitation of CCR5 and CXCR4 by HIV-1 During the Symptomatic Phase of Infection 274
13.5. General Principles of HIV-1 Entry 275
13.6. Signi.cance of HIV-1 gp120-Induced Chemokine Receptor Signaling 281
13.7. Chemokines in HIV-1 Infection 283
13.8. Conclusions 287
Acknowledgments 287
References 287
14 Chemokines and Their Receptors in Fibrosis (Glenda Trujillo and Cory M. Hogaboam) 304
Glenda Trujillo and Cory M. Hogaboam 304
14.1. Introduction 305
14.2. Fibrosis: Is It Linked to In.ammation? 305
14.3. Chemokines and Their Role in Fibrotic Disease 311
14.4. Evidence from Human Studies 317
14.5. Current Therapy for Treatment 318
14.6. Conclusions 319
References 319
15 Chemokines and Angiogenesis (Michael P. Keane, John A. Belperio, and Robert M. Strieter) 327
15.1. Introduction 327
15.2. The CXC Chemokines 329
15.3. Conclusions 337
Acknowledgments 337
References 337
16 Chemokine Receptors in Cancer: Pathobiology and Potential Therapeutic Targets (Tonya C. Walser and Amy M. Fulton) 342
16.1. Introduction 342
16.2. CXC Chemokine Receptors 343
16.3. CC Chemokine Receptors 346
16.4. Other CXC Chemokine Receptors 348
16.5. Other CC Chemokine Receptors 349
16.6. Conclusions 351
Acknowledgments 352
References 352
17 Chemokine Receptors in Neuroinflammation (Astrid E. Cardona and Richard M. Ransohoff) 357
17.1. Introduction 357
17.2. Chemokines and Chemokine Receptors 358
17.3. Expression of Chemokine Receptors in Cells Intrinsic to the Central Nervous System 360
17.4. CXCR4/CXCL12 Linked to CNS Development, and Much More 361
17.5. CXCR2/CXCL1: Role in Oligodendrocyte Development 362
17.6. CX3CR1/CX3CL1: A Complex and Enigmatic System 363
17.7. CXCR3/CCL21 Inducible System of Microglial/ Neuronal Communication 368
17.8. Conclusions 368
References 369
18 Pharmaceutical Targeting of Chemokine Receptors (Sofia Ribeiro and Richard Horuk) 376
18.1. Introduction 376
18.2. Promiscuity of Chemokines and Their Receptors 378
18.3. Targeting Chemokine Receptors 378
18.4. How Successful Have These Approaches Been? 385
18.5. Chemokine Receptors Are Targetable but Are They Good Targets? 388
18.6. How Relevant Are Heterodimers as Disease Targets? 390
18.7. Conclusions 391
References 392
Index 396