Biological Response Mediators and Modulators (eBook)

Front Cover 1
Biological Response Mediators and Modulators 4
Copyright Page 5
Table of Contents 8
Contributors 12
Preface 16
Acknowledgments 20
CHAPTER 1. RECEPTOR-MEDIATED ENDOCYTOSIS AS EXEMPLIFIED BY THE LOW DENSITY LIPOPROTEIN RECEPTOR 22
General Characteristics of Receptor-Mediated Endocytosis 22
Pathway of Receptor-Mediated Endocytosis: The LDL Receptor 24
Mechanism by Which LDL Receptors Reach Coated Pits 25
Recycling of the LDL Receptor 26
Functional Domains of the LDL Receptor: Biosynthesis Studies 26
References 27
CHAPTER 2. THE RECEPTOR FOR EGF FUNCTIONS AS A TYROSINE-SPECIFIC PROTEIN KINASE 28
References 32
CHAPTER 3. REGULATION OF INSULIN RECEPTOR METABOLISM: MECHANISM OF INSULIN-INDUCED RECEPTOR DOWN-REGULATION 34
Change in Insulin Receptor Level Induced by Insulin 35
Synthetic and Degradative Rates of Insulin Receptor in Control and Down-regulated Cells 38
Effect of Insulin-Induced Down-Regulation on Insulin-Stimulated [1-14C]12-Deoxyglucose Transport 44
Characterization of Cell Surface Insulin Receptor Cross-linked Covalently to 1 2 5I-Insulin 44
Rate of Appearance of Heavy Receptors at and Loss of Light Receptors from the Plasma Membrane Following the Shift of Cells to Heavy Amino Acids 47
Effect of Insulin on the Rates of Appearance of Newly-Synthesized Receptor at and the Net Removal of Previously-Synthesized Receptors from the Cell Surface 50
Discussion 54
Acknowledgments 58
References 59
CHAPTER 4. METABOLISM OF ARACHIDONIC ACID BY THE CYCLOOXYGENASE PATHWAY IN MAST CELLS AND BY THE 15- LIPOXYGENASE PATHWAY IN HUMAN EOSINOPHILS 62
Acknowledgments 68
References 68
CHAPTER 5. PHYSIOLOGIC AND PATHOBIOLOGIC EFFECTS OF LEUKOTRIENES C4, D4, AND E4 70
Arachidonic Acid Metabolism in the 5-lipoxygenase Pathway 70
Biological Effects on the Leukotrienes 71
Cell Sources of the Leukotrienes 74
Acknowledgment 75
References 75
CHAPTER 6. BIOLOGICAL ACTVITIES OF LEUKOTRIENE B4 AND OTHER HYDROXYEICOSATETRAENOIC ACIDS (HETEs) 80
Formation of Leukotriene B* and Other Hydroxyeicosatetraenoic Acids 80
Biological Activities of Leukotriene B4 and Other Hydroxyeicosatetraenoic Acids 81
Conclusions 85
References 86
CHAPTER 7. ACETYL GLYCERYL ETHER PHOSPHORYLCHOLINE (AGEPC) A MODEL ANAPHYLACTOMIMETIC MEDIATOR 88
Anaphylactomimetic Mediators 88
Vasoactive Activity of AGEPC 91
Smooth Muscle Contracting Activities of AGEPC 92
AGEPC-induced Systemic Anaphylactoid Reactions 93
Concluding Remarks 98
Acknowledgments 100
References 102
CHAPTER 8. THE ROLE OF LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID IN INFLAMMATORY EVENTS MEDIATED BY HUMAN BASOPHILS AND MAST CELLS 104
Methods and Results 105
The Effect of Lipoxygenase Products on Histamine Release from Human Basophils and Mast Cells 105
The Modulation of Histamine Release from Human Basophils and Mast Cells 111
Discussion 114
Acknowledgments 116
References 116
CHAPTER 9. THE CHEMISTRY AND BIOLOGY OF C3a, C4a, AND C5a AND THEIR EFFECTS ON CELLS 120
Correlations Between Anaphylatoxin Structure and Function 122
A Duality of Anaphylatoxin Action on Pulmonary Tissue 125
Duality of the Action of Anaphylatoxinsin Immunoregulation 132
Summary and Conclusion 136
Acknowledgments 136
References 136
CHAPTER 10. ON THE SIZE HETEROGENEITY AND MOLECULAR COMPOSITION OF THE TRANS-MEMBRANE CHANNELS PRODUCED BY COMPLEMENT 138
Initial Indication from Electrical Conductance Experiments that Complement Channels are Heterogeneous with Respect to Size 140
Molecular Sieving Estimates of the Maximal Size of C5b-8 and C5b-9 Channels 141
Studies of the Heterogeneity of C5b-9 Channels by Molecular Sieving with Paired Markers 145
The Relation Between Channel Size and the Molecular Composition of the C5b-9 Complex 146
Functional Analysis of the Number of C5b6, C7, C8, and C9 Molecules Required for a Single Channel 148
Disappearance of Small Channels at High C9 Multiplicity 152
Models of Channel Structure 155
Summary 158
Acknowledgments 158
References 159
CHAPTER 11. MEMBRANE DAMAGE BY COMPLEMENT COMPONENTS C5b-C9: BIOCHEMICAL AND ULTRASTRUCTURAL STUDIES 162
Nomenclature 164
Properties of Fluid-phase Terminal Complement Complexes 164
Subunit Composition 165
Amphiphilic Properties 168
Molecular Weight 171
Ultrastructure and Membrane Orientation 173
Is the Unit Complement Lesion a C5b~9 Monomer or Dimer? 176
Mechanism of Membrane Damage by C5b-9(m) 177
Perspectives 180
Acknowledgments 181
References 181
CHSPTER 12. CYTOKINE-CELL INTERACTIONS THAT MODULATE INFLAMMATORY REACTIONS 184
Interleukin 1 (IL-1) 186
Colony Stimulating Factors 192
Interleukin 2 (IL-2) 192
Interferon 193
Sequential Cytokine-Cell Interactions 193
Immunopharmacological Implications 194
References 196
CHAPTER 13. INTERLEUKIN-2 AND THE REGULATION OF CYTOTOXIC CELLS 198
Results 199
Discussion 202
References 203
CHAPTER 14. PHARMACOLOGICAL MODULATIONS OF IgE-BINDING FACTOR 206
Formation of IgE-potentiating Factors and IgE-suppressive Factors by Lymph Node Cells of Rats Infected with Nippostrongylus brasiliensis 206
Pharmacologie Modulation of IgE-binding Factors 209
Participation of Lipomodulin in the Selective Formation of IgE-suppressive Factors by Complete Freund's Adjuvant Treatment 212
Summary 216
Acknowledgments 217
References 217
CHAPTER 15. MECHANISMS OF ANTIVIRAL ACTION OF INTERFERONS 220
Antiviral Actions of Interferons 221
Sensitivity of Various Cell Lines to Interferon 225
DNA Viruses and Interferons 226
Interferon-induced Enzymes and Cell Growth 227
Summary 227
References 228
CHAPTER 16. PHARMACOLOGICAL MANIPULATION OF THE CHEMOTACTIC FACTOR RECEPTOR ON LEUKOCYTES 232
Summary 239
References 240
CHAPTER 17. SECRETORY PRODUCTS IN CYTOTOXICITY 242
T Cells 244
NK Cells and K Cells 248
Granulocytes 249
Macrophages 249
Conclusions 255
Acknowledgments 257
References 257
CHAPTER 18. ANTIBODY-MEDIATED TUMOR SUPPRESSION: POSSIBLE ROLE OF LYSOPHOSPHATIDYLCHOLINE AND INTERLEUKIN 262
Lysophosphatidylcholine 264
Interleukin 267
Concluding Remarks 269
Acknowledgments 270
References 270
Index 272