The Reticuloendothelial

System A COMPREHENSIVE TREATISE

Volume 78 Physiology

The Reticuloendothelial System A COMPREHENSIVE TREATISE

General Editors: Herman Friedman, University of South Florida, Tampa, Florida

Mario Escobar, Medical College of Virginia, Richmond, Virginia

and Sherwood M. Reichard, Medical College of Georgia, Augusta, Georgia

MORPHOLOGY Edited by Ian Carr and W. T. Daems

BIOCHEMISTRY AND METABOLISM Edited by Anthony J. Sbarra and Robert R. Strauss

PHYLOGENY AND ONTOGENY Edited by Nicholas Cohen and M. Michael Sigel

IMMUNOPATHOLOGY Edited by Noel R. Rose and Benjamin V. Siegel

CANCER Edited by Herman Friedman and Ronald B. Herberman

IMMUNOLOGY Edited by Joseph A. Bellanti and Herbert B. Herscowitz

PHYSIOLOGY (In two parts) Edited by Sherwood M. Reichard and James P. Filkins

PHARMACOLOGY Edited by John Hadden, Jack R. Battisto, and Andor Szentivanyi

HYPERSENSITIVITY Edited by S. Michael Phillips and Peter Abramoff

INFECTION Edited by John P. Utz and Mario R. Escobar

The Reticuloendothelial

System A COMPREHENSIVE TREATISE

Volume 7B Physiology

Edited by SHERWOOD M. REICHARD

Medical College of Georgia Augusta, Georgia

and

JAMES P. FILKINS Loyola University Medical Center

Maywood, Illinois

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

Main entry under title:

The Reticuloendothelial system.

Includes bibliographies and indexes. CONTENTS: v. 1. Carr, I., Daems, W. T., and Lobo, A. Morphology.-v. 2.

Biochemistry and metabolism-[etc.]-v. 7. Reichard, S. M. and Filkins, J. P. Physiology.

1. Reticulo-endothelial system. 2. Macrophages. I. Friedman, Herman, 1931-II. Escobar, Mario E. III. Reichard, Sherwood M. [DNLM: 1. Reticuloendothelial sys­tem. WH650 R437] QP115.R47 591.2'95 79-25933

ISBN-13: 978-1-4612-9441-2 DOl: 10.1007/978-1-4613-2353-2

© 1985 Plenum Press, New York

e-ISBN-13: 978-1-4613-2353-2

Soll:cover reprint of the hardcover 1st edition 1985

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved

No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

Contributors

BURTON M. ALTURA • Department of Physiology, State University of New York, Downstate Medical Center, Brooklyn, New York

MARCO BAGGIOLINI • Theodor Kocher Institute, University of Bern, Bern, Switzerland

HARRY A. BERNHEIM • Department of Biology, Tufts University, Medford, Massachusetts

L. JOE BERRY • Department of Microbiology, The University of Texas, Austin, Texas

R. J. BONNEY • Departments of Immunology and Infla,mmation, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey

JOHN W. B. BRADFIELD • Department of Pathology, University of Bristol, Bristol, England

JOSEPH D. BRAIN • Department of Environmental Science and Physiology, Har­vard University School of Public Health, Boston, Massachusetts

JULIA W. BUCHANAN • Division of Nuclear Medicine, The Johns Hopkins Medi­cal Institutions, Baltimore, Maryland

HARVEY R. COLTEN • Division of Cell Biology, Department of Medicine, Chil­dren's Hospital Medical Center, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts

P. DAVIES • Departments of Immunology and Inflammation, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey

LOIS B. EpSTEIN • Cancer Research Institute and Department of Pediatrics, Uni­versity of California, San Francisco, California

R. ALAN B. EZEKOWITZ • Sir William Dunn School of Pathology, University of Oxford, Oxford, England

K. B. P. FLEMMING • Institute of Biophysics and Radiobiology, University of Freiburg, Freiburg, West Germany

v

vi CONTRIBUTORS

SIAMON GORDON • Sir William Dunn School of Pathology, University of Ox­ford, Oxford, England

G. HORPACSY • Institute for Experimental Medicine, University of Cologne, Co­logne, West Germany

J. L. HUMES • Departments of Immunology and Inflammation, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey

RALPH F. KAMPSCHMIDT • Biomedical Division, The Samuel Roberts Noble Foundation, Inc., Ardmore, Oklahoma

F. A. KUEHL, JR. • Department of Biochemistry, Merck Sharp and Dohme Re­search Laboratories, Rahway, New Jersey

HEINRICH LIEHR • Medical Department I, Academic Hospital, Saarbriicken­Winterberg, West Germany

DAVID O. LUCAS • Department of Microbiology, College of Medicine, Univer­sity of Arizona, Tucson, Arizona

ROGER H. MITCHELL • Biomedical Division, The Samuel Roberts Noble Founda­tion, Inc., Ardmore, Oklahoma

ROBERT N. MOORE • Department of Microbiology, The University of Tennessee, Knoxville, Tennessee

JOHN W. REBUCK • Department of Pathology, The Henry Ford Hospital, De­troit, Michigan

ANDY C. REESE • Department of Cell and Molecular Biology, Medical College of Georgia, Augusta, Georgia

SHERWOOD M. REICHARD • Departments of Radiology and Physiology, Medical College of Georgia, Augusta, Georgia

THOMAS M. SABA • Department of Physiology, Albany Medical College of Union University, Albany, New York

ROBERT C. STRUNK • Department of Pediatrics, National Jewish Hospital and Research Center/National Asthma Center, and Department of Pediatrics, University of Colorado Medical School, Denver, Colorado

HENRY N. WAGNER, JR. • Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Foreword

This comprehensive treatise on the reticuloendothelial system is a project jointly shared by individual members of the Reticuloendothelial (RE) Society and bio­medical scientists in general who are interested in the intricate system of cells and molecular moieties derived from those cells which constitute the RES. It may now be more fashionable in some quarters to consider these cells as part of what is called the mononuclear phagocytic system or the lymphoreticular sys­tem. Nevertheless, because of historical developments and current interest in the subject by investigators from many diverse areas, it seems advantageous to present in one comprehensive treatise current information and knowledge con­cerning basic aspects of the RES, such as morphology, biochemistry, phylogeny and ontogeny, physiology, and pharmacology as well as clinical areas including immunopathology, cancer, infectious diseases, allergy, and hypersensitivity. It is anticipated that by presenting information concerning these apparently het­erogeneous topics under the unifying umbrella of the RES attention will be focused on the similarities as well as interactions among the cell types constitut­ing the RES from the viewpoint of various disciplines. The treatise editors and their editorial board, consisting predominantly of the editors of individual vol­umes, are extremely grateful for the enthusiastic cooperation and enormous task undertaken by members of the biomedical community in general and especially by members of the American as well as European and Japanese Reticuloen­dothelial Societies. The assistance, cooperation, and great support from the editorial staff of Plenum Press are also valued greatly. It is hoped that this unique treatise, the first to offer a fully comprehensive treatment of our knowl­edge concerning the RES, will provide a unified framework for evaluating what is known and what still has to be investigated in this actively growing field. The various volumes of this treatise provide extensive in-depth and integrated infor­mation on classical as well as experimental aspects of the RES. It is expected that these volumes will serve as a major reference for day-to-day examination of various subjects dealing with the RES from many different viewpoints.

Herman Friedman Mario R. Escobar

Sherwood M. Reichard

vii

Introduction

The physiology of any body system-be it the cardiovascular, endocrine, body fluid, pulmonary, etc.-embraces three categories of functional analysis:

1. The fundamental mechanisms of the system. 2. The regulation of the mechanisms by either intrinsic or extrinsic influences. 3. The coordinated interactions of the system in the integration of total orga­

nismic functions.

Thus, this treatise on the physiology of the reticuloendothelial system by definition will focus on the mechanisms, regulation, and integrative role of the body macrophage system.

While the phagocytic or more properly endocytic functions-which for many years almost exclusively defined the RES-are given predominant atten­tion, the current state of the growing body of knowledge on RES exocytosis, i.e., secretory functions of the macrophages, is thoroughly reviewed.

The clinical physiology of the RES has also been included, since the applica­tion of basic knowledge to the prevention of human disease is the goal of all biomedical investigation.

The vast knowledge of the functions of the RES as influencing immune functions, host defense in infection, and neoplasia has been omitted, since these areas will be developed in other volumes of this treatise.

Herman Friedman Mario R. Escobar

Sherwood M. Reichard

ix

Preface

Physiology is divided into two volumes. Volume 7 A covered the funda­mental mechanisms and regulation of phagocytosis, regulatory interac­tions with blood elements, and regulatory interactions with blood metabolites and constituents, providing the fundamental physiology and pathophysiology of the RES necessary to progress into the contents of this volume.

This volume (7B) is divided into three sections: IV. Regulation and Mac­rophage Secretions; V. Clinical Physiology of the RES; and VI. Integrative Func-tions of the RES. .

The chapters in the first section of Volume 7B (Section IV) review the excit­ing new knowledge concerned with the secretory functions of the macrophage. These include the endocrinelike activities of the RES (Moore and Berry); the control of complement synthesis by monocytes and macrophages (Strunk and Colter); the cellular mechanisms by which arachidonic acid oxygenation prod­ucts are formed in macrophage populations (Davies et al.); the properties of the lysosomal system of macro phages and the process of their secretion (Baggiolini); the nature, regulation, and role of macrophage neutral proteinases with particu­lar attention given to plasminogen activators and their markers (Gordon and Ezekowitz); the role of macrophages in the production of interferon and the effects of interferon on macrophages (Lucas and Epstein); and the activity of a protein, leukocytic endogenous mediator, synthesized by macrophages as an intermediate in acute phase changes in infection, trauma, neoplastic disease, and other stresses.

Section V deals with the clinical physiology of the RES and emphasizes the methods currently available for the measurement of RES clearance in man (Brad­field); the role of altered RES function in liver pathophysiology (Liehr); the use of nuclear imaging of the RES in clinical medicine to reveal global and regional phagocytic function (Buchanan and Wagner); the inflammatory cell dynamics in man (Rebuck); and the role of plasma opsonic fibronectin in nonspecific re­ticuloendothelial host defense, particularly septic shock (Saba).

Section VI summarizes some of the important integrative functions of the RES, including the role of pulmonary macrophages, their protective posture, and their part in the pathogenesis of pulmonary diseases (Brain); the production of leukocyte pyrogen by phagocytic cells of liver and spleen during most infec­tious states (Bernheim); the relationship of RES function to the integrity of the microcirculation, its dysfunction in circulatory shock and trauma (Altura); the effect of radiation on phagocytic cell activity and on certain aspects of the func­tions of the RES in homeostasis, particularly in relation to radiation protection mechanisms (Flemming and Reichard); the role of the RES in the pathophysio­logy of shock, the factors released by shock induced mechanisms and the inad­vertent use of mediators in the etiology of the shock state (Reichard and Reese);

xi

xii PREFACE

the generation of the complement system and toxic oxygen products in inflam­mation and shock (Reichard); and the turnover of lysosomal enzymes in shock and the role of the RES in the balance of these circulatory enzymes (Horpacsy).

We gratefully acknowledge the authors who accepted the difficult task of summarizing the state of knowledge in these rapidly evolving areas of current investigation.

Sherwood M. Reichard James P. Filkins

Contents

IV. Regulation and Macrophage Secretions

1. Endocrinelike Activities of the RES: An Overview

ROBERT N. MOORE and L. JOE BERRY

1. Introduction 3 2. Macrophage Factors Regulating Lymphocyte Functions 4

2.1. Interleukin 1 (Lymphocyte-Activating Factor) 4 2.2. Thymic Maturation Factor 5 2.3. Genetically Related Factor 6 2.4. Interferon 6 2.5. Glucocorticoid Response-Modifying Factor 7 2.6. Prostaglandins and Oxygen Metabolites 7

3. Macrophage Factors Regulating Nonlymphoid Cells 8 3.1. Leukocytic Endogenous Mediator (Endogenous Pyrogen) 8 3.2. Synovial Cell- and Chondrocyte-Stimulating Factors 9 3.3. Serum Amyloid A-Inducing Factor 9 3.4. Fibroblast-Activating Factor and Corneal Cell Factor 9 3.5. Glucocorticoid-Antagonizing Factor and Macrophage Insulinlike

Activity 10 4. Macrophage Factors Regulating Cells of the RES 12

4.1. Colony-Stimulating Factor and Factor Inducing Monocytopoiesis 12

4.2. Interferon 14 4.3. Prostaglandins 15

5. Concluding Remarks 15 References 18

2. Regulation of Complement Synthesis in Mononuclear Phagocytes

ROBERT C. STRUNK and HARVEY R. COL TEN

1. Introduction 25 2. Historical 27 3. Systems Used to Assay for Synthesis of Complement Proteins 28 4. Regulation of Complement Synthesis by Mononuclear

Phagocytes 31

xiii

xiv CONTENTS

4.1. Posttranslational Modification 31 4.2. Effect of Agents Used to Induce a Peritoneal Exudate 33 4.3. Percentage of Mononuclear Phagocytes That Synthesize

Complement 34 4.4. Effect of Phagocytosis 35 4.5. Kinetics of Complement Production by Human Peripheral Blood

Monocytes and the Effect of Lymphokine on the Rate and Extent of Production 36

4.6. Effect of Culture Surfaces on Capacity of Macrophages and Monocytes to Produce Complement 37

4.7. Effect of Cortisone and Cyclophosphamide 39 4.8. Alteration of Complement Synthesis during Disease States 40 4.9. Miscellaneous 41

References 42

3. The Synthesis of Arachidonic Acid Oxygenation Products by Macrophages

P. DAVIES, R. J. BONNEY, J. L. HUMES, and F. A. KUEHL, JR.

1. Introduction 47 2. Synthesis of Arachidonic Acid Oxygenation Products via the

Cyclooxygenase Pathway in Mononuclear Phagocytes 50 2.1. Mouse Peritoneal Macrophages 50 2.2. Regulation of Prostaglandin Synthesis by Mouse Peritoneal

Macrophages 53 2.3. The Phospholipases of Mouse Peritoneal Macrophages 54 2.4. Prostaglandin Synthesis by Mouse Peritoneal Macrophages Is

Dependent on RNA and Protein Synthesis 54 2.5. Variations in the Nature and Extent of Cyclooxygenase Product

Formation by Resident and Elicited Mouse Peritoneal Macrophages and Mononuclear Phagocytes from Other Sources in the Mouse 55

2.6. The Synthesis of Products of the Cyclooxygenase Pathway by Human Peripheral Blood Monocytes 57

3. Synthesis of Lipoxygenase Pathway Products by Macrophages 58 4. Concluding Remarks 63

References 64

4. Lysosomal Hydrolases

MARCO BAGGIOLINI

1. Introduction 67

CONTENTS XV

2. The Monocyte Granules 67 3. From Monocytes to Macrophages 68 4. The Lysosomal Apparatus of Macrophages 69

4.1. Introduction 69 4.2. Subcellular Fractionation of Alveolar Macrophages 70 4.3. Subcellular Fractionation of Peritoneal Macrophages and Bone

Marrow-Derived Macrophages 72 4.4. Ultrastructure of Alveolar and Peritoneal Macrophages 73

5. Lysosomal Enzyme Levels in Differentiating Macrophages 75 6. The Release of Lysosomal Enzymes from Macrophages 77

6.1. Release into Phagocytic Vacuoles 80 6.2. Release by Secretion 80

7. Stimulus-Induced Secretion of Lysosomal Enzymes 81 7.1. Induction by Phagocytosis 81 7.2. Induction by Nonphagocytic Stimuli 84 7.3. The Mechanism of Lysosomal Enzyme Secretion by

Macrophages 86 References 88

5. Macrophage Neutral Proteinases: Nature, Regulation, and Role

SIAM ON GORDON and R. ALAN B. EZEKOWITZ

1. Introduction 95 2. Nature of Macrophage Neutral Proteinases 97

2.1. Background 97 2.2. General Aspects 97 2.3. Plasminogen Activator 99

3. Localization of Macrophage Neutral Proteinases 110 3.1. General Considerations 110 3.2. Plasminogen Activator 110

4. Regulation of Neutral Proteinase Activities in Macrophages 112 4.1. General Considerations 112 4.2. Inflammation 113 4.3. Endotoxin 114 4.4. Surface Receptors and Endocytosis 115 4.5. Immune Regulation 118 4.6. Colony-Stimulating Factors 120 4.7. Hormonal and Pharmacological Control 121 4.8. Proteinases, Peptides, and Antiproteinases 124

5. Role of Proteinase in Macrophage Function 125 5.1. General Comments 125 5.2. Fibrinolysis 125 5.3. Activation of Plasma Proteinase Cascades 126 5.4. Catabolism of Connective Tissue and Other Proteins 127

xvi CONTENTS

5.5. Cell Surfaces, Adherence, and Endocytosis 127 5.6. Macrophage Activation 128 5.7. Macrophage Proliferation 129 5.8. Prostaglandin Synthesis 130

6. Addendum 130 7. Conclusion 131

References 132

6. Interferon and Macrophages

DAVID O. LUCAS and LOIS B. EpSTEIN

1. Introduction 143 2. Macrophages as Producers of Interferon 144 3. Inducers for Macrophage Interferon Production 145 4. Importance of the Degree of Maturation of the Macrophage for

Interferon Production 147 5. Relationships of Macrophage Interferon to Other Macrophage

Products 148 6. Kinetics and Process of Interferon Induction in Macrophages 7. The Macrophage as an Accessory Cell for Interferon Production

150 151

8. The Role of Macrophages for in Vivo Interferon Production 153 9. Effects of Interferon on Macrophages 154

10. Concluding Comments 158 References 160

7. Leukocytic Endogenous Mediator in Nonspecific Host Defenses

ROGER H. MITCHELL and RALPH F. KAMPSCHMIDT

1. Introduction 169 2. Isolation of LEM and Its Physiochemical Properties 170

2.1. Isolation and Purification 170 2.2. Physiochemical Properties 170 2.3. Differentiation from Bacterial Endotoxin 171

3. Comparison of LEM to IL-l and EP 171 4. Cells and Conditions Involved in Production and Release of

LEM 172 4.1. Cells Which Produce LEM 172 4.2. Activation of Cells to Release LEM 173 4.3. Synthesis and Release Conditions 174

5. Biological Activities of LEM 174 5.1. Neutrophilia and Granulopoiesis 174 5.2. Zinc Metabolism 175

CONTENTS xvii

5.3. Iron Metabolism 176 5.4. Copper Metabolism 177 5.5. Acute-Phase Proteins 177 5.6. Protection against Bacterial Infection 179 5.7. Other Biological Activities 180

6. Summary 180 References 180

V. Clinical Physiology of the RES

8. Evaluation of RES Clearances in Man

JOHN W. B. BRADFIELD

1. Introduction 189 2. Methods Available for Evaluation of RES Clearances in Man 192

2.1. Detection and Measurement of Spillover of Endogenous Substances 192

2.2. Clearance of Exogenous Test Particles Injected Intravenously 197

2.3. Investigation of Stages in RES Clearances 207 3. Conclusions 211

References 212

9. RES Function in Experimental and Human Liver Disease

HEINRICH LIEHR

1. Introduction 223 2. RES Function in Experimental Liver Disease Related to Human

Abnormalities 223 2.1. Acute Liver Disease 223 2.2. Chronic Liver Disease 229 2.3. Summary: Influence of Experimental Liver Disease on RES

Function 232 3. RES Function in Human Liver Disease 233

3.1. RES Function and Acute Liver Disease 233 3.2. RES Function and Acute Alcoholic Liver Disease 235 3.3. RES Function and Chronic Liver Disease 236

4. Summary and Perspective 240 References 241

xviii CONTENTS

10. Regional Phagocytosis in Man

JULIA W. BUCHANAN and HENRY N. WAGNER, JR.

1. Introduction 247 2. The Liver 247

2.1. Radiopharmaceuticals 247 2.2. The Normal Liver 249 2.3. The Liver Scan in Disease 250

3. The Spleen 255 3.1. Radiopharmaceuticals 255 3.2. The Normal Spleen 256 3.3. The Spleen Scan in Disease 256

4. Bone Marrow 260 4.1. Radiopharmaceuticals 260 4.2. The Normal Bone Marrow 261 4.3. Bone Marrow Scans in Disease 261

5. The Lymph System 263 5.1. Radiopharmaceuticals 263 5.2. The Normal Lymph Node 263 5.3. Lymph Node Imaging in Disease 264

References 264

11. Inflammatory Cell Dynamics in Man

JOHN W. REBUCK

1. Definitions 271 1.1. Acute Inflammation Due to Trauma 271 1.2. Acute Immune Response in Inflammation 273 1.3. The Lymphocyte in Man 275 1.4. The Monocyte in Man 276

2. Observations on the Cell-Mediated Immune Response and the Sequence of Leukocytic Migrations 276 2.1. The Acute Immune Response in Inflammation in Man 276 2.2. Phagocytic Activity of Transforming Lymphocytes in Inflammation

in Man 278 3. Critique 279

3.1. Immunological Dissection of Leukocytic Inflammatory Responses in Skin Windows in Man 279

3.2. Leukocytic Responses to Abnormal Inflammatory Stimuli 280 3.3. Abnormal Leukocytic Responses to Normal Inflammatory

Stimuli 281 4. Discussion 282

CONTENTS xix

4.1. Neutrophilic Functions 282 4.2. The Monocyte of Man in Inflammation 282 4.3. The Lymphocyte in Man: Amplification and Dynamism in

Inflammation 283 5. Summary 284

References 285

12. Fibronectin and Reticuloendothelial Clearance of Blood-Borne Particles: Clinical Studies in Septic Shock

THOMAS M. SABA

1. Introduction 289 2. Opsonic Glycoprotein (Plasma Fibronectin) Depletion and Particulate

Removal 290 3. Reticuloendothelial Systemic Defense and Traumatic Injury 294 4. Organ Failure in Shock and RE Function 295 5. Opsonic <x2-SB Glycoprotein and Plasma Fibronectin 297 6. Cell Surface Fibronectin as Related to Plasma Fibronectin 298 7. Cryoprecipitate Infusion and Organ Function in Septic Injured

Patients 301 8. Microvascular Fluid and Solute Exchange and Fibronectin 302 9. Antibacterial Defense by Phagocytosis and Fibronectin 305

10. Conclusions and Significance 306 References 308

VI. Integrative Functions of the RES

13. Physiology and Pathophysiology of Pulmonary Macrophages

JOSEPH D. BRAIN

1. Introduction 315 2. Types of Pulmonary Macrophages 315 3. Origin of Pulmonary Macrophages 316 4. Fate of Pulmonary Macrophages 318 5. Quantitation and Harvesting Techniques 319 6. Role of Pulmonary Macrophages 323 7. Pathophysiology of Pulmonary Macrophages 327 8. Conclusion 332

References 332

xx CONTENTS

14. Temperature Regulation and Fever

HARRY A. BERNHEIM

1. Introduction 339 2. Basic Thermal Physiology 339 3. Neuronal Integration during Fever 341

3.1. General Consideration 341 3.2. The CNS and Fever 342

4. Leukocyte Pyrogen 342 4.1. Characteristics 342 4.2. Nonpyrogenic Effects of LP 343 4.3. Immune Fever 344 4.4. LP as a Monokine 345

5. Cell Sources of LP 346 5.1. Historical Background 346 5.2. Characteristics of LP Release from Mononuclear Phagocytes 346 5.3. Kupffer Cells 347

6. Summary 348 References 348

15. Microcirculatory Regulation and Dysfunction: Relationship to RES Function and Resistance to Shock and Trauma

BURTON M. ALTURA

1. Introduction 355 2. Microcirculation 357

2.1. Architecture, Ultrastructure, and Density of Adrenergic Innervation 357

2.2. Function and Regulation 361 2.3. Criteria for a Substance to Be Classified a Local Regulator of Blood

Flow 363 2.4. Important Candidates for Regulators of Blood Flow 364

3. Microcirculatory Dysfunction in Circulatory Shock and Trauma 366 3.1. Failure of Local Vascular-Homeostatic Mechanisms 366 3.2. Vasoactive Mediators in Circulatory Shock and Low-Flow

States 368 4. RE Cell Function in Recognition and Treatment of Circulatory Shock

and Trauma 376 4.1. Overview of Circulatory Shock Problem 376 4.2. RES Phagocytic Function as a Tissue-Level Index of the Course of

Shock and Low-Flow State Syndrome 377 4.3. RES-Stimulating Materials Compatible for Human Use:

Prophylactic Treatment for Circulatory Shock 380 5. Specific RE Cell-Microcirculatory Interactions in Shock, Trauma, and

Systemic Stress 382

CONTENTS xxi

5.1. RE Cell Colloid Stimulants Prevent Loss of Venular Tone in Circulatory Shock and Trauma 383

5.2. Estrogenic and Glucocorticoid Steroids Normalize Microvascular Tone in Circulatory Shock and Trauma: Temporal Relationship to Effects on the RES 384

5.3. Vasoactive Peptide Pressor Analogs with Selective Microvascular Actions Improve Survival and RE Cell Function in Shock and Trauma Syndromes 385

6. Conclusions 386 References 388

16. Radiation Effects on Phagocytic Cells of the RES

K. B. P. FLEMMING and SHERWOOD M. REICHARD

1. Introduction 397 2. Alterations of RES Cell Structure 397 3. Changes of Phagocytic Cell Function 398

3.1. Irradiation in Vitro 398 3.2. Irradiation in Vivo 399

4. Changes of Global RES Phagocytic Function 403 4.1. Inorganic Colloids: Chromium Phosphate, Saccharated Iron Oxide,

Radiogold, Thorotrast, Prodigiosin 403 4.2. Carbon Clearance 405

5. Handling of Bacteria and Antigens by Macrophages 408 5.1. Bacterial Clearance 408 5.2. Intracellular Digestive Function of Macrophages 409

6. Presentation of Antigen 411 7. Biochemical Properties 412 8. Altered Response of the RES in Whole-Body-Irradiated Animals 412

8.1. Alteration in Drug Response 412 8.2. Enhancement of Particle-Induced RES Blockade 413 8.3. Potentiation of the Response to Stress 413 8.4. Mechanisms of Depression of RES Response 414

9. Oxygen Metabolism 415 10. Protection against Radiation Lethality 417 11. Conclusion 418 References 419

17. Role of the Reticuloendothelial System in Shock

SHERWOOD M. REICHARD and ANDY C. REESE

1. Introduction 429 2. Evidence for RES Involvement in Shock 431

xxii CONTENTS

2.1. General Observations 431 2.2. RES Blockade 431 2.3. RES Stimulation 432 2.4. RES Activity in Shock 433 2.5. Effect of Macrophage Heterogeneity on Responses to

Trauma 435 2.6. Role of the RES in Immune Suppression following Traumatic

Shock 435 2.7. Effect of Trauma on RE Cells in the Lung 436 2.8. Effect of Adrenal Cortical Hormones on RES Function following

Trauma 438 2.9. Effect of Other Hormones on RES Function following

Trauma 439 2.10. Effect of Trauma on RE Cell Energy Metabolism 439 2.11. Effect of Starvation on Susceptibility to Shock Induction 440 2.12. Effect of Cancer on Susceptibility to Shock Induction 441

3. Effect of Trauma-Sensitive Factors on RES and Shock Induction 3.1. Role of Lysosomal Enzymes in the Pathogenesis of Shock 3.2. Effect of Released Tissue Debris on RES Function 442 3.3. Effect of Fibronectin Depletion on RES Function 443 3.4. RE Cell Depressant Substance 443 3.5. Role of Prostaglandins in Shock 444 3.6. Toxic Oxygen Products 446

4. Regulatory Role of Trauma-Sensitive Serum Factors on RES Activity 447 4.1. C-Reactive Protein 448 4.2. Ceruloplasmin 449 4.3. Role of Fibronectin in Shock 449

441 442

4.4. The Effect of Complement Activation on Shock Induction and RES Function 452

4.5. Trauma-Protecting Factors 454 4.6. Histamine 457

5. Summary: Mechanism of Shock Induction and Protective Activity of the RES 460

References 462

18. Toxic Oxygen Products in Shock

SHERWOOD M. REICHARD

1. Introduction 475 2. Toxic Oxygen Products 476

2.1. Cytotoxic Action 477 2.2. Inactivation of Antiproteases 477 2.3. Prostaglandin, Thromboxane, and Leukotriene Generation 478

3. Protective Mechanisms against Toxic Oxygen Products 479 3.1. Plasma Factors 479 3.2. Cellular Factors 480

4. Glutathione 481 4.1. Glutathione Deficiencies 4.2. Traumatic Shock 483

5. Addition of Scavengers 486 5.1. Glutathione 486 5.2. Superoxide Dismutase 5.3. Other Radical Scavengers 5.4. Corticosteroids 487

6. Complement Activation 488 7. Shock Induction 489

7.1. Anaphylatoxins 489 7.2. Toxic Oxygen Products

8. Summary 490 References 491

482

487 487

489

CONTENTS xxiii

19. The RES and the Turnover of Circulating Lysosomal Enzymes in Shock

G. HORPACSY

1. Introduction 499 2. Release of Lysosomal Enzymes in Shock 499

2.1. RE Function, Shock Tolerance, and Enzyme Release 500 2.2. Role of Single Organs in Enzyme Turnover 503 2.3. Cellular Origin of Lysosomal Enzymes 504

3. RES and Enzyme Elimination 505 3.1. Lysosomal Enzymes as Shock Toxins 506 3.2. Clinical Evidence for Enzyme Elimination 508 3.3. Hepatic Receptors and Clearance of Lysosomal Enzymes 511

4. Balance of Circulating Lysosomal Enzymes 514 5. Summary 516

References 516

Index 521

Contents of Volume 7 A

I. Fundamental Mechanisms and Regulation of Phagocytosis

1. Surface Forces in Phagocytosis

CAREL J. VAN 055, DARRYL R. ABSOLOM, and A. WILHELM NEUMANN

2. Regulation of Mononuclear Phagocyte Proliferation

CARLETON C. STEWART

3. Quantitation of Macrophage Phagocytosis in Vitro

PAUL W. GUDEWICZ

4. Kinetics of Vascular Clearance of Particles by Phagocytes

SIGURD J. NORMANN

5. Vascular Clearance of Microorganisms

R. J. MOON

6. RES Control of Endotoxemia

HENRY GANS

II. Regulatory Interactions with the Blood Elements

7. The Reticuloendothelial System and Erythropoiesis

BRIAN A. NAUGHTON and ALBERT S. GORDON

8. Erythroclasia and Bilirubin Metabolism

JOHN C. NELSON, NADER G. IBRAHAM, and RICHARD D. LEVERE

9. Hemostasis

LAURENCE A. SHERMAN and JOHN E. KAPLAN

10. Platelets

JOHN E. KAPLAN and DUDLEY G. MOON

xxv

xxvi CONTENTS OF VOLUME 7A

11. RES-Leukocyte Interactions

MARC FELDMANN, DAVID R. KATZ, and GEOFFREY H. SUNSHINE

III. Regulatory Interactions with Blood Metabolites and Constituents

12. Glucose Regulation and the RES

JAMES P. FILKINS

13. Interaction of the Reticuloendothelial System with Blood Lipid and Lipoprotein Metabolism

T. J. C. VAN BERKEL, P. H. E. GROOT, and A. VAN TOL

14. Selected Aspects of Protein Metabolism in Relation to Reticuloendothelial System, Lymphocyte, and Fibroblast Function

MICHAEL C. POWANDA and ELIZABETH D. MOYER

15. Iron Metabolism

FARID I. HAURANI and SAMIR K. BALLAS

16. Lead and Cadmium: Effect on Host Defense Mechanisms and Toxic Interactions with Bacterial Endotoxins

JAMES A. COOK, W. J. DOUGHERTY, W. C. WISE, and P. V. HALUSHKA

Index