Chemokine Biology - Basic Research and Clinical Application (eBook)

Contents 6
List of contributors 8
Preface 11
Chemokines in animal disease models 13
Chemokines in animal models of inflammation 14
Introduction 14
Experimental acute systemic inflammation (sepsis) 15
Experimental granulomatous lung inflammation 19
Experimental asthma 20
Rheumatoid arthritis 22
Conclusion 24
References 24
Introduction 29
Experimental autoimmune encephalomyelitis 29
Experimental autoimmune diabetes 31
Autoimmune diseases 29
Summary 32
References 33
Chemokines in allergic responses: eosinophils, basophils, mast cells 37
Introduction 37
Eosinophils, basophils and mast cells play a key role in allergic inflammation through the function of their chemokines and chemokine receptors 38
Eosinophils, basophils and mast cells link innate and adaptive immunity during allergic inflammation: Role of chemokines and chemokine receptors 40
Eosinophils, basophils and mast cells skew the adaptive immune response to new antigens towards Th2 inflammation: Role of chemokines and chemokine receptors 42
Eosinophils basophils and mast cells amplify the allergic response through the function of their chemokines 44
References 47
Chemokines as drug targets 52
Chemokines as drug targets 53
Introduction 53
Pharmaceutical drug development: Small molecule inhibitors 56
Biotechnology drug development: Protein therapeutics 60
Perspectives 62
References 63
Screening and characterization of cyclic pentapeptide CXCR4 antagonists/inverse agonists using a pheromone responsive reporter gene in Saccharomyces cerevisiae: Utility of G protein coupled receptor constitutively active mutants 68
Introduction 68
Materials and methods 70
Results 71
Discussion 79
References 81
Antagonists of CXCR3: a review of current progress 85
Introduction 85
Small molecule antagonists of CXCR3 88
Neutralizing antibodies 88
Modified ligands 89
Conclusion 90
References 90
IL-8 receptor antagonist: basic research and clinical utility 95
Introduction 95
Utility of CXCL8 antagonists in basic research 96
Potential role and utility of CXCR2 antagonists in disease 98
Airways inflammation in premature infants 101
References 103
Current status of CCR1 antagonists in clinical trials 109
Introduction 109
Evidence for the role of CCR1 in rheumatoid arthritis 110
Evidence for the role of CCR1 in multiple sclerosis 110
Evidence for role of CCR1 in other diseases 111
Small molecule antagonists of CCR1 111
BX471 (ZK-811752) 111
CP-481,715 113
Issues and challenges to the development of chemokine receptor antagonists 114
Conclusion 115
References 115
Small molecule CCR2 antagonists 120
Introduction 120
CCR2 antagonists in development 122
ucb-102405 122
References 127
Chemokine axes in hematopoietic stem cell mobilization 129
Introduction: Hematopoietic stem cell mobilization 129
The chemokine axis 130
Concluding remarks 139
References 140
CCR5 antagonists: from discovery to clinical efficacy 149
Introduction 149
CCR5 antagonists prior to human efficacy studies 150
CCR5 antagonists reaching human efficacy studies 155
Conclusion 161
References 161
Index 168