The Chemokine System in Experimental and Clinical Hematology (Current Topics in Microbiology and Immunology Book 341)

The aim of the issue is to describe and explain the importance of the chemokine system in hematology. As described in the introduction the chemokine system is probably important for many aspects of normal as well as malignant hematopoiesis. A major focus is the development and treatment of hematologic malignancies, including the immunobiology of stem cell transplantation.” The present reviews illustrate that chemokines can be involved in leukemogenesis. The chemokine system is also important both for the crosstalk between malignant cells and their neighbouring nonmalignant stromal cells (including endothelial cells) as well as for immunoregulation in patients treated with allogeneic stem cell transplantation. Thus, chemokines are important both for the pathogenesis and treatment of hematological diseases. Preface 6 Contents 8 The Chemokine System in Experimental and Clinical Hematology 13 1 The Chemokine System 14 1.1 Nomenclature 14 1.2 Chemokines 15 1.3 Chemokine Receptors 16 2 Chemotaxis of Immunocompetent Cells 16 3 Chemokines in Normal and Leukemic Hematopoiesis 17 3.1 Effects of Chemokines on Normal Hematopoiesis 17 3.2 Angiogenesis in the Development of Hematological Malignancies 17 4 Humoral Immune Responses Against Cytokines and Cytokine Receptors: The Relevance for the Chemokine System 18 5 The Chemokine System in Clinical Hematology 19 5.1 Inhibition of Chemokine Responses 19 5.1.1 Anticancer Treatment 19 5.1.2 Immunosuppressive Therapy 19 5.2 Enhancement of Chemokine Responses 20 5.3 Biomarkers of Cancer 20 6 Conclusion 20 References 21 Chemokine Decoy Receptors: Structure-Function and Biological Properties 25 1 The Chemokine Universe 26 2 Regulation of the Chemokine System 27 3 Chemokine Decoy Receptors 28 3.1 D6 29 3.2 DARC 30 3.3 CCRL2 31 3.4 CCX-CKR 31 3.5 CXCR7 32 4 Chemokine Decoy Receptors Mechanism of Action 33 4.1 Receptor Internalization 33 4.2 Recycling 34 4.3 Structural Motifs and Trafficking Adapters 34 5 Chemokine Decoy Receptors in Action 35 5.1 Role in Inflammation 35 5.2 Role in Tumor Biology 38 6 Concluding Remarks 40 References 40 Role of Chemokines in the Biology of Natural Killer Cells 47 1 Natural Killer Cells 48 1.1 NK Cell Distribution into Various Tissues 49 1.2 Role of NK Cells in Hemopoietic Stem Cell Transplantation 49 1.3 NK Cells in Tumor Immunology 50 2 Chemokines 51 2.1 Expression of Receptors for Chemokines in NK Cells 52 2.2 Effect of Chemokines on the In Vitro NK Cell Chemotaxis 53 2.3 Effect of Chemokines on the In Situ Accumulation of NK Cells Under Resting Conditions 53 2.3.1 Trafficking into the Peripheral LNs 53 2.3.2 Localization of NK Cells in the Bone Marrow and Their Egress from This Organ 54 2.3.3 Trafficking into Decidual and Adenoid Tissues 54 2.4 Role of Chemokines/Chemokine Receptors in the Sojourn of NK Cells at the Sites of Inflammation 55 2.4.1 Trafficking into Sites of Tumor Growth 55 2.4.2 Trafficking into Sites of Infections 56 2.4.3 Trafficking into the Skin and Other Inflammatory Sites 57 2.5 Role of Chemokines in the Accumulation of NK Cells at Autoimmune Sites 57 2.5.1 Trafficking into the Synovial Fluids 57 2.5.2 Trafficking into Inflamed Liver 58 2.5.3 Trafficking into Inflamed Brains 58 2.6 Trafficking into Target Organs of GvH Disease 59 3 Summary and Concluding Remarks 60 References 62 Chemokines in Angiogenesis 69 1 Introduction 70 2 The Chemokine Network 71 3 Angiostatic Chemokines 73 3.1 ELR-Negative CXCR3-Ligands Are Angiostatic 74 3.2 Regulation of Angiostatic Chemokines: Coupling to Immune Response 74 3.3 Angiostatic CXCR3-Ligands in Tumor Growth and Angiogenesis 75 4 Angiogenic Chemokines 76 4.1 ELR-Positive CXC-Family Chemokines Induce Angiogenesis 76 4.2 Pro-Angiogenic ELR-Positive Chemokines Are Induced Downstream of NF-kB Activation 77 4.3 The CXCR2L/CXCR2 Axis in Tumor Vascularization 77 4.4 CXCL12/CXCR4 Signaling in Recruitment of Pro-Angiogenic Bone Marrow Derived Cells 78 4.5 CCL-Family Chemokines as Inducers of Angiogenesis 80 4.5.1 CCL2 in Arteriogenesis and Angiogenesis 81 4.6 CX3CL/CX3CR Axis in Angiogenesis 81 4.7 KSHV-Encoded and CMV-Encoded Chemokines in Angiogenesis 82 5 The Chemokines and Their Receptors as Future Therapeutic Targets 82 References 84 Genetic Polymorphisms in the Cytokine and Chemokine System: Their Possible Importance in Allogeneic Stem Cell Transplantation 93 1 General Introduction 94 2 Hematopoietic Stem Cell Transplantation 95 2.1 Invasive Aspergillosis 95 3 Chemokine Response During Fungal Infections 96 3.1 Association of Polymorphisms in Chemokine Genes with Invasive Fungal Infection 97 4 Graft vs. Host Disease 98 4.1 SNPs in Cytokine and Chemokine Genes Associated with GvHD 98 4.2 Genetic Markers in Cytokine Receptor and Chemokine Receptor Genes Associated with GvHD 100 5 SNPs in Adaptive Immunity 102 6 Ethnicity and SNP Frequencies 103 7 Conclusion 103 References 104 The Chemokine System: A Possible Therapeutic Target in Acute Graft Versus Host Disease 107 1 Introduction 108 2 Allogeneic Hematopoetic Stem Cell Transplantation and Graft Versus Host Disease 108 3 The Chemokine-Chemokine-Receptor System 111 4 The Role of the Chemokine-Chemokine-Receptor System in aGVHD 111 4.1 Chemokines and aGVHD of the Gastrointestinal Tract 113 4.2 Chemokines and aGVHD of the Liver 115 4.3 Chemokines and aGVHD of the Skin 116 4.4 Chemokines and aGVHD of the Lung 117 5 The Role of the Chemokine-Chemokine Receptor System in cGVHD 119 6 Current Possibilities and Perspectives for Targeting the Chemokine-Chemokine Receptor System in GVHD 120 References 122 Homing in on Acute Graft vs. Host Disease: Tissue-Specific T Regulatory and Th17 Cells 131 1 Introduction 133 1.1 Acute Graft vs. Host Disease 133 1.2 T Cells and aGVHD 134 2 Immunology of aGVHD 135 2.1 Model of Interactions 135 2.2 Lymph Node Physiology 136 2.3 Lymphocyte Compartmentalization 136 3 Tregs, aGVHD, and Adhesion Molecules 138 3.1 History of Suppressor Cells 138 3.2 Natural Treg Phenotype and Characterization 138 3.3 Foxp3 Expression 139 3.4 Treg Mechanisms of Action 139 3.5 Tregs and Murine aGVHD 140 3.6 Graft vs. Tumor Concerns 142 3.7 Tregs and Human aGVHD 142 3.8 Adhesion Molecules and Tissue-Specific Tregs 145 3.9 Recent Work on Tissue-Specific Tregs and aGVHD 146 3.10 Summary of Tregs and aGVHD 147 4 Th17 Cells and aGVHD 147 4.1 Biology of Th17 Cells 147 4.2 Th17 Cells and CCRs 148 4.3 Th17 Cells and the aGVHD Disease Process 149 5 Summary 149 References 150 The Chemokine Network in Acute Myelogenous Leukemia: Molecular Mechanisms Involved in Leukemogenesis and Therapeutic Implications 159 1 Introduction 160 2 Primary Human AML Cells Often Show Constitutive Chemokine Release 161 2.1 Constitutive Chemokine Release by Primary Human AML Cells 161 2.2 Modulation of the Constitutive Chemokine Release 162 2.2.1 Differentiation Induction 163 2.2.2 Tissue Oxygenation 163 2.2.3 Pharmacological Interventions 163 2.2.4 Nonleukemic Stromal Cells 164 2.2.5 Cellular Immune Responses 165 3 Chemokine Receptors on Primary Human AML Cells 165 4 The CXCL12/CXCR4 System in Human AML 167 4.1 CXCR4 and CXCL12 Expression in AML Bone Marrow 167 4.2 Biological Effects of CXCR4-Initiated Signaling in AML 167 4.3 CXCR4/CXCL12 Has a Prognostic Impact in Human AML 168 4.4 CXCR4 as a Possible Therapeutic Target in Human AML 169 5 Leukemogenesis Through Transcriptional Regulation in the Chemokine System 169 6 Chemokine Serum Levels in AML 170 7 Chemotaxis of Immunocompetent Cells in Human AML 171 7.1 T Cell Chemotaxis 171 7.2 Chemotaxis of Regulatory T Cells 171 7.3 Chemotaxis of Monocytes 172 7.4 Chemotaxis of Natural Killer Cells 172 8 Chemokine-Mediated Suppression of Normal Hematopoiesis 173 9 Concluding Remarks 174 References 176 CXCR4 in Clinical Hematology 183 1 Introduction 184 2 Mechanism of Action 184 3 Preclinical Models of Mobilization 185 3.1 Additional Potential Uses Suggested by Preclinical Models 186 4 Clinical Uses of Inhibition of CXCR4 in Hematologic Diseases 187 4.1 The Present Indications 187 4.1.1 Plerixafor Alone for Stem Cell Mobilization 188 4.1.2 Plerixafor Plus G-CSF to Mobilize Stem Cells 188 4.1.3 Efficacy of Plerixafor Plus G-CSF for Mobilization of Stem Cells 189 4.1.4 Plerixafor for Poor Mobilizers 190 4.1.5 Safety of Plerixafor 191 4.1.6 Assessment of Cancer Cell Contamination 192 4.1.7 Characterization of Human Cells Mobilized with Plerixafor +/- G-CSF 192 4.2 Potential Future Indications 193 4.2.1 Congenital Neutropenias: (Example: WHIM Syndrome) 193 4.2.2 Expanding the Application of Mobilizing Agents in Cancer Treatment: Improving the Effectiveness of Chemotherapy to Treat. 194 5 Conclusions 195 References 195 Immunobiology of Heparin-Induced Thrombocytopenia 203 1 Introduction 204 2 Clinical Characteristics 204 3 Diagnostic Issues 205 3.1 Clinical Scoring System for HIT 205 3.2 Laboratory Evaluation of HIT 206 4 Treatment of HIT 207 5 Immunobiology of HIT 208 6 Disclosure of Interests 210 References 210 Index 213 3642126383,9783642126383,9783642126390 Springer Part I. Introduction.-- Chemokine System In Experimental And Clinical Hematology / Oystein Bruserud, Astrid Olsnes Kittang.-- Part Ii. Experimental Hematology.-- Chemokine Decoy Receptors: Strucuture-function And Biological Properties / Raffaella Bonecchi, Benedetta Savino, Elena M. Borroni, Alberto Mantovani, Massimo Locati.-- Role Of Chemokines In The Biology Of Natural Killer Cells / Azzram A. Maghazachi.-- Chemokines In Angiogenesis / Anna Dimbert.-- Part Iii. Immunobiology Of Allogeneic Stem Cell Transplantation.-- Genetic Polymorphisms In The Cytokine And Chemokine Systems: Their Possible Importance In Allogeneic Stem Cell Transplantation / Jeurgen Loeffler, Michael Ok, Oliver C. Morton, Markus Mezger, Hermann Einsele.-- Chemokine System: A Possible Therapeutic Target In Acute Graft Versus Host Disease / Nicolai A. Kittan, Gerhard C. Hildebrandt.-- Homing In On Acute Graft Vs. Host Disease: Tissue-specific T Regulatory And Th17 Cells / Brian G. Engelhardt, James E. Crowe Jr.-- Part Iv: Clinical Hematology.-- Chemokine Network In Acute Myelogenous Leukemia: Molecular Mechanisms Involved In Leukemogenesis And Therapeutic Implications / Astrid Olsnes Kittang, Kimberley Hatfield, Kristoffer Sand, Hakon Reikvam, Oystein Bruserud.-- Cxcr4 In Clinical Hematology / Gary Calandra, Gary Bridger, Simon Fricker.-- Immunobiology Of Herparin-induced Thrombocytopenia / Per Morten Sandset. Øystein Bruserud, Editor. Includes Bibliographical References And Index. Front Matter....Pages i-xi The Chemokine System in Experimental and Clinical Hematology....Pages 3-12 Chemokine Decoy Receptors: Structure–Function and Biological Properties....Pages 15-36 Role of Chemokines in the Biology of Natural Killer Cells....Pages 37-58 Chemokines in Angiogenesis....Pages 59-80 Genetic Polymorphisms in the Cytokine and Chemokine System: Their Possible Importance in Allogeneic Stem Cell Transplantation....Pages 83-96 The Chemokine System: A Possible Therapeutic Target in Acute Graft Versus Host Disease....Pages 97-120 Homing in on Acute Graft vs. Host Disease: Tissue-Specific T Regulatory and Th17 Cells....Pages 121-146 The Chemokine Network in Acute Myelogenous Leukemia: Molecular Mechanisms Involved in Leukemogenesis and Therapeutic Implications....Pages 149-172 CXCR4 in Clinical Hematology....Pages 173-191 Immunobiology of Heparin-Induced Thrombocytopenia....Pages 193-202 Back Matter....Pages 203-206