The vertebrate blood-gas barrier in health and disease : structure, development, and remodeling

This comprehensive volume on the blood-gas barrier (BGB) among vertebrates covers its structure and composition along with aspects of evolution, bioengineering, and morphometry. The book also discusses the embryological development of the BGB, including chronology of events and molecular control in vertebrates; modulation of the barrier function, including cyclic stretch-induced increases in alveolar epithelial permeability; mechanisms of lung vascular/epithelial permeability; transport mechanisms of the BGB, including sodium transport channels; factors affecting trans-barrier traffic of fluids, such as chronic elevation of pulmonary microvascular pressure; stress failure; regulation and repair in acute lung injury; chronic lung disease; and lung transportation. Ten authoritative chapters approach the blood-gas barrier holistically, from basic structure and development to pathology and treatment. Properties of the BGB are discussed in the earlier chapters, followed by prenatal and post-natal development and mechanisms of the healthy BGB. The latter half of the book delves into the pathology of the BGB, analyzing common afflictions and exploring options for treatment, including its alterations during lung transplantation. Intuitively structured and comprehensive, __The Vertebrate Blood-Gas Barrier in Health and Disease__ is ideal for researchers and clinicians interested in pneumology and angiology. Preface 5 References 9 Contents 10 Contributors 12 Chapter-1 14 Generalities of Gas Diffusion Applied to the Vertebrate Blood–Gas Barrier 14 1.1 Introduction 14 1.2 Why Diffusion? 15 1.3 Gas Diffusion 18 1.3.1 Fickʼs Laws of Diffusion 18 1.3.2 Gas Diffusion in Liquids 20 1.3.3 Gas Capacitance 22 1.4 Some Considerations 22 1.4.1 Thickness (θ) and Area (A) of the BGB 22 1.4.2 Diffusion (D) and Permeation (K) Coefficients 24 1.4.3 The Environmental Side of the BGB 25 References 26 Chapter-2 28 Morphological and Morphometric Properties of the Blood-Gas Barrier: Comparative Perspectives 28 2.1 Introduction 28 2.1.1 Cellular Organisation of the Lung Parenchyma 30 2.1.2 Structure of the Blood-Gas Barrier 36 2.1.3 Sporadic Attenuation of the Blood-Gas Barrier 38 2.1.4 Exposure of Pulmonary Capillary Blood to Air 40 2.1.5 Morphometry of the Blood-Gas Barrier 44 References 48 Chapter-3 52 Prenatal and Postnatal Development of the Vertebrate Blood–Gas Barrier 52 3.1 Overview of Vertebrate Lung Development 53 3.2 Biological Design of the Blood–Gas Barrier in Vertebrates 53 3.3 Embryonic Formation of the Blood–Gas Barrier 54 3.3.1 Development of the Mammalian Blood–Gas Barrier 54 3.3.1.1 Prenatal Formation of the Mammalian Blood–Gas Barrier 54 3.3.1.2 Perinatal Developmental of the Mammalian Blood–Gas Barrier 57 3.3.2 Development of the Avian Blood–Gas Barrier 57 3.3.2.1 Cell Decapitation by Constriction or Squeezing (Peremerecytosis) 58 3.3.2.2 Cell Cutting by Cavitation or Double Membrane Unzipping (Secarecytosis) 60 3.3.2.2.1 Cell Cutting by Intracellular Space Formation 60 3.3.2.2.2 Cell Cutting by Double Membrane Unzipping 63 3.4 Mechanisms of Epithelial Cell Attenuation 64 3.5 Molecular Regulation of Blood–Gas Barrier Development 65 3.5.1 Molecular Regulation of Blood–Gas Barrier Development in Mammals 66 3.5.1.1 Growth Factors 66 3.5.1.2 Transforming Growth Factor-β 67 3.5.2 Transcription Factors and Nuclear Receptors 67 3.5.2.1 GATA-6 Transcription Factor 67 3.5.2.2 Forkhead Orthologs (FOX) Transcription Factors 68 3.5.2.3 Thyroid Transcription Factor (TTF-1) 68 3.5.2.4 Hypoxia-Inducible Factor 2α (HIF2α) 68 3.5.2.5 Notch 69 3.5.2.6 Glucocorticoid Receptor and Retinoic Acid 69 3.5.2.7 E74-Like Factor 5 (ELF5) 70 3.5.2.8 Wnt/β-Catenin 70 3.5.3 Other Molecular Signals 71 3.5.3.1 Semaphorin 3A 71 3.5.3.2 Connexin 43 71 3.5.3.3 T1 Alpha 71 3.6 Molecular Regulation of BGB Formation in Other Vertebrates 72 3.7 Conclusion 72 References 73 Chapter-4 78 Molecular Mechanisms Regulating the Pulmonary Blood–Gas Barrier 78 4.1 The Structure of Junctional Complexes Regulating Barrier Function in the Lung 78 4.2 Molecular Mechanisms that Modulate the BGB 82 4.3 Environmental Factors Affecting the BGB 87 4.4 Conclusion 90 References 91 Chapter-5 98 Barrier Enhancing Signals 98 5.1 Introduction 100 5.2 Role of Cell–Cell Adhesions Junctions in Regulating Endothelial/Epithelial Barrier Function 100 5.2.1 Structure of AJs 100 5.2.2 VE-Cadherin Structure 101 5.2.3 Barrier Enhancement via VE-Cadherin 103 5.2.3.1 p120 Catenin-Mediated VE-Cadherin Enhancement 103 5.2.3.2 β-Catenin and Plakoglobin-Mediated VE-Cadherin Enhancement 104 5.3 Protein Tyrosine Phosphatases (PTPs)-Mediated AJ Enhancement 105 5.4 Small GTPases-Mediated Barrier Enhancement 106 5.4.1 Rac1-Mediated Barrier Enhancement Signaling 107 5.4.2 Cdc42-Mediated Barrier Enhancement Signaling 110 5.4.2.1 Rap1-Mediated Barrier Enhancement Signaling 110 5.5 Tight Junction-Mediated Barrier Enhancement Signaling 112 5.5.1 Occludins 112 5.5.2 Claudins 113 5.5.3 JAM 114 5.5.4 ZO Proteins 114 5.6 Focal Adhesion-Mediated Barrier Enhancement Signaling 115 5.6.1 Integrin-Mediated Barrier Enhancement 115 5.6.2 Focal Adhesion Kinase-Mediated Barrier Enhancement 116 5.7 Conclusions 118 References 118 Chapter-6 127 Transbarrier Ion and Fluid Transport 127 6.1 Introduction 128 6.1.1 Overview of the Structure and Function of the Alveolar Epithelium 128 6.1.2 Generalized Paradigm for Transbarrier Ion and Fluid Transport 130 6.1.3 Bioelectric Properties of the Alveolar Epithelium 131 6.1.3.1 Epithelial Sodium Channel (ENaC) 131 6.1.3.2 Na/K ATPases 132 6.1.3.3 Chloride Channels 132 6.1.3.4 Potassium Channels 133 6.1.3.5 Aquaporins 133 6.1.4 Summary of Transbarrier Transport of Salt and Water 134 6.1.5 Transbarrier Transport in Lung Disease 134 6.1.5.1 The Importance of Oxidative Stress in Lung Disease 135 6.1.5.2 Acute Respiratory Distress Syndrome (ARDS) 135 6.1.5.3 Pulmonary Edema in ARDS 135 6.1.5.4 Cystic Fibrosis (CF) 138 6.1.5.5 Chronic Lung Disease 139 6.1.6 Summary of Transbarrier Transport in Lung Disease 140 References 141 Chapter-7 146 Stress Failure of the Pulmonary Blood–Gas Barrier 146 7.1 Introduction 146 7.2 Ultrastructure of the Blood–Gas Barrier 146 7.3 The Structural Dilemma of the Blood–Gas Barrier 149 7.4 What Component of the Blood–Gas Barrier is Responsible for Its Strength? 150 7.5 What Stress Is Required to Produce Failure of the Blood–Gas Barrier? 154 7.6 Stress Failure of the Blood–Gas Barrier Under Physiological Conditions 156 7.7 Stress Failure Under Pathological Conditions 158 7.8 Remodeling of Pulmonary Capillaries 161 7.9 Comparative Physiology of the Blood–Gas Barrier 163 References 166 Chapter-8 170 The Lung Endothelial Barrier in Acute Inflammation 170 8.1 Introduction 171 8.2 Pulmonary Endothelial Barrier Disruption 173 8.3 Role of Neutrophils, Monocytes and Thrombocytes in Pulmonary Endothelial Barrier Disruption 174 8.4 Complement and Coagulation Systems and Vascular Permeability 176 8.5 Role of Toll-like Receptor 4 in the Regulation of Pulmonary Vascular Permeability 178 8.6 The Angiopoietin/Tie2 System 179 8.7 Sphingosine-1-Phosphate and other Biologically Active Sphingolipids 181 8.8 Role of Reactive Oxygen and Nitrogen Species in the Pathogenesis of Lung Injury 183 8.9 Adrenomedullin (AM) and Endothelial Barrier Function 185 8.10 Stem Cells in Lung Injury 187 8.11 Conclusions and Future Perspectives 188 References 189 Chapter-9 199 Lung Transplantation and the Blood-Gas Barrier 199 9.1 Introduction 200 9.2 Evaluation of BGB Function After Transplantation 200 9.2.1 Physiological and Biochemical Parameters 200 9.2.2 Structural Parameters 201 9.3 Blood-Gas Barrier Stress During Transplantation 202 9.4 IR Injury and the BGB 204 9.4.1 Definition, Incidence, and Clinical Relevance 204 9.4.2 Morphology and Physiology of IR Injury 204 9.4.2.1 Alveolar Epithelium 205 9.4.2.2 Surfactant 207 9.4.2.3 Septal Interstitium 208 9.4.2.4 Endothelium 208 9.4.2.5 Pulmonary Edema 208 9.4.2.6 Cell Death 209 9.4.2.7 Inflammatory Cell Infiltration and Activation 211 9.4.2.8 Mediators of IR Injury 211 9.4.3 Prevention, Management, and Therapy of IR Injury 211 9.4.3.1 Donor Selection and Management 215 9.4.3.2 Lung Preservation 216 9.4.3.3 Recipient Management 217 9.4.3.4 Ex Vivo Lung Perfusion (EVLP) 218 9.4.4 Long-Term Effects of IR Injury 219 9.5 Acute Allograft Rejection and the BGB 219 9.6 Chronic Lung Allograft Dysfunction (CLAD) and the BGB 220 9.7 Final Remarks 221 References 222 Chapter-10 231 Stereological Studies on Transient Gas Exchangers with Emphasis on the Structure and Function of the Human Placenta in Normal and Compromised Pregnancies 231 10.1 Introduction 231 10.2 The Amniote Plan—Structural Overview of Egg and Placenta 232 10.3 The Human Placenta and Its O2 Environment 233 10.4 The Human Placenta and Its Structural Variation Across Normal Gestation 234 10.5 Relative Growth Rates of Placental Compartments 235 10.6 The Significance of these Gestational Changes for Transplacental Exchange 237 10.7 The Human Placenta and Morphometric Estimators of DO2 238 10.7.1 Estimating Partial Conductances 240 10.7.2 Stereological Variables 241 10.8 Variation of DpO2 of the Human Placenta During Normal Pregnancy 242 10.8.1 Does the Placenta have a Functional Reserve Capacity? 243 10.8.2 Predictions Based on Morphometric DpO2 Changes 243 10.9 Morphometric DpO2 and DvmO2 in Complicated Human Pregnancies 244 10.10 Concluding Remarks 246 References 247 Index 251 This comprehensive volume on the blood-gas barrier (BGB) among vertebrates covers its structure and composition along with aspects of evolution, bioengineering, and morphometry. The book also discusses the embryological development of the BGB, including chronology of events and molecular control in vertebrates; modulation of the barrier function, including cyclic stretch-induced increases in alveolar epithelial permeability; mechanisms of lung vascular/epithelial permeability; transport mechanisms of the BGB, including sodium transport channels; factors affecting trans-barrier traffic of fluids, such as chronic elevation of pulmonary microvascular pressure; stress failure; regulation and repair in acute lung injury; chronic lung disease; and lung transportation. Ten authoritative chapters approach the blood-gas barrier holistically, from basic structure and development to pathology and treatment. Properties of the ℗lBGB are discussed in the earlier chapters, followed by prenatal and post-natal development and mechanisms of the healthy BGB. The latter half of the book delves into the pathology of the ℗lBGB, analyzing common afflictions and exploring options for treatment, including its alterations during lung transplantation. Intuitively structured and comprehensive, The Vertebrate Blood-Gas Barrier in Health and Disease is ideal for researchers and clinicians interested in pneumology and angiology Front Matter....Pages i-xiv Generalities of Gas Diffusion Applied to the Vertebrate Blood–Gas Barrier....Pages 1-14 Morphological and Morphometric Properties of the Blood-Gas Barrier: Comparative Perspectives....Pages 15-38 Prenatal and Postnatal Development of the Vertebrate Blood–Gas Barrier....Pages 39-64 Molecular Mechanisms Regulating the Pulmonary Blood–Gas Barrier....Pages 65-84 Barrier Enhancing Signals....Pages 85-113 Transbarrier Ion and Fluid Transport....Pages 115-133 Stress Failure of the Pulmonary Blood–Gas Barrier....Pages 135-158 The Lung Endothelial Barrier in Acute Inflammation....Pages 159-187 Lung Transplantation and the Blood–Gas Barrier....Pages 189-220 Stereological Studies on Transient Gas Exchangers with Emphasis on the Structure and Function of the Human Placenta in Normal and Compromised Pregnancies....Pages 221-240 Back Matter....Pages 241-243