The Reticuloendothel ial

System A COMPREHENSIVE TREA TISE

Volume 7A Physiology

The Reticuloendothelial System A COMPREHENSIVE TREATISE

General Editors: Herman Friedman, University 0/ South Florida, Tampa, Florida

Mario Escobar, Medical College 0/ Virginia, Richmond, Virginia

and Sherwood M. Reichard, Medical College 0/ Georgia, Augusta, Georgia

MORPHOLOGY Edited by lan 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 TREA TISE

Volume 7A Physiology

Edited by

SHERWOOD M. REICHARD Medical College oj Georgia

Augusta, Georgia

and

JAMES P. FILKINS Loyola University Medical Center

Maywood, IIlinois

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

Main entry under tide:

The Reticuloendothelial system.

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

Biochemistry and metabolism-[etc.]-v. 7A Physiology. 1. Reticulo-endothelial system. 2. Macrophages. I. Friedman, Herman, 1931-

11. Escobar, Mario E. 111. Reichard, Sherwood M. [DNLM: 1. Reticuloendothelial sys­tem. WH650 R437] QP1l5.R47 591.2'95 79-25933

ISBN 978-1-4684-4576-3 ISBN 978-1-4684-4574-9 (eBook)

DOI 10.1007/978-1-4684-4574-9

©1984 Plenum Press, New York Softcover reprint of the hardcover 1 st edition 1984 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, mechanicaI, photocopying, rnicrofilming, recording, or otherwise, without written permission from the Publisher

Contributors

DARRYL R. ABSOLOM • Immunochemistry Laboratory, Department of Micro­biology, State University of New York, Buffalo, New York, and Research Institute, The Hospital for Sick Children, Toronto, and Department of Me­chanical Engineering, University of Toronto, Toronto, Ontario, Canada

SAMIR K. BALLAS • Cardeza Foundation for Hematologic Research, Depart­ment of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania

JAMES A. COOK • Department of Physiology, Medical University of South Carolina, Charleston, South Carolina

w. J. DOUGHERTY • Department of Anatomy, Medical University of South Carolina, Charleston, South Carolina

MARC FELDMANN • ICRF Tumour Immunology Unit, Department of Zoology, University College London, London, England

JAMES P. FILKINS • Department of Physiology, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois

HENRY GANS • Surgical, Research, and Pathology Services of the Danville Veterans Administration Medical Center, and University of Illinois School of Basic Medical Science and Clinical Medicine, and Division of Nutritional Sciences, College of Agriculture, University of Illinois at Urbana, Urbana, Illinois

ALBERT S. GORDON • Department of Biology, New York University, New York, New York

P. H. E. GROOT • Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands

PAUL W. GUDEWICZ • Department of Physiology, Albany Medical College of Union University, Albany, New York

P. V. HALUSHKA • Departments of Pharmacology and Medicine, Medical Uni­versity of South Carolina, Charleston, South Carolina

v

vi CONTRIBUTORS

FARID I. HAURANI • Cardeza Foundation for Hematologic Research, Depart­me nt of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania

NADER G. IBRAHAM • Department of Medicine, New York Medical College, Valhalla, New York

JOHN E. KAPLAN • Department of Physiology, Albany Medical College of Union University, Albany, New York

DAVID R. KATZ • Department of Pathology, The Middlesex Hospital Medical School, London, England

RICHARD D. LEVERE • Department of Medicine, New York Medical College, Valhalla, New York

DUDLEY G. Mo ON • Department of Physiology, Albany Medical College of Union University, Albany, New York

R. J. Mo ON • Division of Basic Sciences, School of Medicine, Mercer Univer­sity, Macon, Georgia

EUZABETH D. MOYER • Departments of Surgery and Biochemistry, State Uni­versity of New York, Buffalo, New York. Present address: Department of In­travenous Nutrition, Cutter Group of Miles Laboratories, Berkeley, California

BRIAN A. NAUGHTON • Department of Biology, New York University, New York, New York

JOHN C. NELSON • Department of Medicine, New York Medical College, Val­halla, New York

A. WILHELM NEUMANN • Research Institute, The Hospital for Sick Children, Toronto, and Department of Mechanical Engineering, University of Toron­to, Toronto, Ontario, Ca na da

SIGURD J. NORMANN • Department of Pathology, College of Medicine, Uni­versity of Florida, Gainesville, Florida

MICHAEL C. POWANDA • Biochemistry Branch, U.S. Army Institute of Surgi­cal Research, Fort Sam Houston, Texas. Present address: Division of Cut­aneous Hazards, Letterman Army Institute of Research, Presidio of San Francisco, California

LAURENCE A. SHERMAN • Missouri/Illinois Regional Red Cross Blood Ser­vices, St. Louis, Missouri

CONTRIBUTORS vii

CARLETON C. STEWART • Experimental Pathology Group, Los Alamos Na­tional Laboratory, Los Alamos, New Mexico

GEOFFREY H. SUNSHINE • ICRF Tumour Immunology Unit, Department of Zoology, University College London, London, England. Present address: De­partment of Surgery, Tufts University Veterinary School, Boston, Massachusetts

T. J. C. VAN BERKEL • Department of Biochemistry I, Medical Faculty, Eras­mus University Rotterdam, Rotterdam, The Netherlands

CAREL J. VAN Oss • Immunochemistry Laboratory, Departments of Microbiol­ogy and Chemical Engineering, State University of New York, Buffalo, New York

A. VAN TOL • Department of Biochemistry I, Medical Faculty, Erasmus Uni­versity Rotterdam, The Netherlands

W. C. WISE • Department of Physiology, Medical University of South Car­olina, Charleston, South Carolina

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 weIl 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 weIl 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 weIl 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 knowedge 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 weIl 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

IX

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

xi

Preface

This volume is divided into three sections: I, Fundamental Mechanisms and Regulation of Phagocytosis; 11, Regulatory Interactions with the Blood Elements; and III, Regulatory Interactions with Blood Metabolites and Constituents.

The first three chapters of Section I develop the cellular physiology of phagocytosis-with special attention to surface forces (van Oss et al.), the fac­tors governing phagocytic proliferation in cultures of macrophages (Stewart), and the available means of quantitation of macrophage phagocytosis in vitra (Gudewicz). The second set of three chapters in Section I is devoted to the mechanisms of phagocytosis in the vascular macrophages and deals with the fundamentals of the kinetics of vascular clearance (Normann), the intravascular phagocytosis of microorganisms (Moon), and the macrophage's role in endotox­emia control (Gans).

Seetion 11 deals with the interaction of the RES with the cellular blood elements and emphasizes macrophage functions in erythropoiesis (Naughton and Gordon), erythroclasia and bilirubin metabolism (Nelson et al.), hemostasis (Sherman and Kaplan), platelet activities (Kaplan and Moon), and leukocyte interaction (Feldmann et al.).

Section III summarizes the current state of knowledge re gar ding RES involvement in the metabolie physiology and pathophysiology of glucose reg­ulation (Filkins), lipid and lipoprotein metabolism (van Berkel et al.), protein metabolism (Powanda and Moyer), iron metabolism (Haurani and Ballas), and lead and cadmium interactions (Cook et al.). Volume A should provide the fundamental physiology and pathophysiology of the RES necessary to progress into the contents of Volume B: macrophage secretory functions and regulation, the clinical physiology of the RES, and integrative function of the RES.

We are grateful to the authors who accepted the difficult task of summariz­ing the state of knowledge in rapidly evolving areas of current investigation.

Sherwood M. Reichard James P. Filkins

xiii

Contents

I. Fundamental Mechanisms and Regulation of Phagocytosis

1. Surface Forces in Phagocytosis

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

1. Introduction 3 2. Thermodynamics of Particle Adhesion and Particle Engulfment 4

2.1. Particle Adhesion 4 2.2. Particle Engulfment 6 2.3. Adhesion and Engulfment in Liquid Media of Lower Surface

Tension Than Saline Water 7 3. Thermodynamics of Protein (Especially IgG) Adsorption 10

3.1. Protein Adsorption and Opsonization 10 3.2. Thermodynamics 10

4. Opsonization 14 4.1. Role of Specific and Aspecific IgG 14 4.2. Smallest Size of Immune Complexes Likely to Be Ingested 15 4.3. Role of Complement and IgM 17 4.4. Other Opsonizing Agents 17 4.5. Role of IgA 17 4.6. Opsonization in Viva 18

5. Pathological Phagocytes 18 6. "Activation" of Macrophages and Other Phagocytes 21 7. Effect of Various Agents on the Surfaces of Phagocytes and/or Bacteria in

Vitra 22 7.1. Agents Mainly Affecting Phagocytes 22 7.2. Agents Mainly Affecting Bacteria 22 7.3. Agents Affecting Both Phagocytes and Bacteria 23

8. Influence of Electrokinetic Surface Potential and of Cell Shape 23 9. Methods for Measuring Surface Tensions of Cells, Particles, and

Proteins 24 9.1. Partition Methods 24 9.2. Contact Angle Methods 25 9.3. Adhesion and Adsorption Methods 26 9.4. Solidification Front Method 27

xv

xvi CONTENTS

9.5. Droplet Sedimentation Method 28 9.6. Phagocytic Ingestion in Liquids of Different Surface

Tensions 28 10. Phagocytosis and Recognition in Vitro and in Vivo 28

10.1. In Vitro Phagocytosis in Aqueous Media 28 10.2. Phagocytosis in Biological Fluids 29 10.3. Recognition 30

References 31

2. Regulation of Mononuclear Phagocyte Proliferation

CARLETON C. STEWART

1. Introduction 37 2. Colony Formation by Murine MNP 38 3. Proliferative Capacity of Peritoneal Exudate Cells 41 4. Proliferative Capacity of Bone Marrow Cells 43 5. Surface Markers on Differentiating MNP 45 6. Consumption of MGF by Macrophages 47 7. Serum Dialyzable Activity 48 8. Growth-Promoting Activity of Erythrocytes 49 9. Inhibition of MNP Proliferation 50

10. Genetics of Colony Formation 51 11. Local Proliferation Revisited 52 References 54

3. Quantitation of Macrophage Phagocytosis in Vitro

PAUL W. GUDEWICZ

1. Introduction 57 2. Sources of Macrophages for in Vitro Phagocytic Studies 58

2.1. Sources of Macrophage Populations 58 2.2. In Vitro Assay Conditions for Phagocytosis 60

3. Test Particles Used for Phagocytosis in Vitro 61 3.1. Artificial Particles 62 3.2. Biological Particles 63

4. Methods to Quantify Phagocytosis in Vitro 64 4.1. Morphological and Bacterial Counting Methods 64 4.2. Radioactive and Chemical Methods 66

5. Summary 67 References 68

CONTENTS xvii

4. Kinetics of Vascular Clearance of Particles by Phagocytes

SIGURD J. N ORMANN

1. Introduction 73 2. Kinetics of Vascular Clearance: A Zero- or First-Order Rate

Equation? 74 3. Vascular Clearance, Surface-Saturation Kinetics, and Phagocytosis 77 4. Derivation of the Particle-Membrane Constant (Kp ) and Maximum

Phagocytic Velocity (V rnax) 78 5. Affinity of Particles for the Phagocyte Surface: The Association Constant

Ka 81 6. Particle Selection and the Clearance Behavior of Different Particles 84

6.1. Particle Stability 84 6.2. Particle Charge 86 6.3. Monodispersity 87 6.4. Summary 87

7. Host Factors Modulating Vascular Clearance 88 7.1. Liver Blood Flow 88 7.2. Species 89 7.3. Kupffer Cell Number 90 7.4. Opsonins 91

8. Clearance Inhibition by Particle Injection 91 8.1. Immediate-Onset RES Paralysis 92 8.2. Delayed-Onset RES Paralysis 93 8.3. Opsonin Depletion 93 8.4. Competitive Inhibition between Particles 94

9. Coda 96 References 97

5. Vascular Clearance of Microorganisms

R. J. MOON

1. Introduction 103 2. In Vivo Studies 103

2.1. Viruses 103 2.2. Bacteria 104 2.3. Fungi 106

3. Liver Perfusion Studies 106 4. Future Directions 109 5. Conclusions 110 References 111

xviii CONTENTS

6. RES Control of Endotoxemia

HENRY GANS

1. Introduction 115 2. Detection of Endotoxin 116 3. Sources of Infection 118 4. Effect of Endotoxin at the Cellular Level 119 5. Endotoxin Transfer across the Normal Gut Wall 120 6. Endotoxin Absorption in Disease 123 7. Enteric Endotoxin's Potentiation of Various Hepatotoxins 125 8. The Role of the Kupffer Cell in Processing Enteric Endotoxins 126 9. Endotoxin-Induced Host Responses 128

10. Host Immune Responses to Endotoxin 132 References 136

H. Regulatory Interactions with the Blood Elements

7. The Reticuloendothelial System and Erythropoiesis

BRIAN A. NAUGHTON and ALBERT S. GORDON

1. Introduction: General Role of the RES in Erythropoiesis 147 2. The Role of the Macrophage in Erythropoiesis 148

2.1. Reticular Cells of the Bone Marrow: Medullary Erythropoiesis 148

2.2. Reticular Cells of the Liver and Spleen: Extramedullary Erythropoiesis 149

2.3. Hormones and Chemical Agents: Relation of the RES to Hematopoiesis 160

References 178

8. Erythroclasia and Bilirubin Metabolism

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

1. Erythrocyte Destruction 189 1.1. The Life Span of the Erythrocyte 189 1.2. Changes in the Aging Erythrocyte 190

CONTENTS XIX

1.3. Sites of Erythrocyte Destruction 194 1.4. Mechanisms of Erythrocyte Destruction 195

2. Hemoglobin and Heme Metabolism 199 2.1. Regulation of Heme Metabolism 199 2.2. Mechanisms of Heme Degradation 203 2.3. Transport, Conjugation, and Excretion of Bilirubin 210

References 212

9. Hemostasis

LAURENCE A. SHERMAN and JOHN E. KAPLAN

1. Introduction 221 2. Clearance of Coagulation System Activators 222 3. Clearance of Procoagulants and Antiproteases 224 4. Clearance of Fibrinogen Derivatives 225 5. Production of Hemostatically Active Substances 228

5.1. Synthesis 228 5.2. Regulation of Synthesis 230

6. Influences of the Coagulation System on the RES 231 7. Conclusion 232 References 232

10. Platelets

JOHN E. KAPLAN and DUDLEY G. MOON

1. Introduction 237 2. Physiology and Anatomy of Platelets 238 3. Phagocytosis of Platelets 239

3.1. Hypersplenie and Thrombocytopenic States 239 3.2. Normal and Thrombotic States 243

4. Recognition of Platelets by the RES 246 4.1. Immune Recognition 246 4.2. Senescent Recognition-Role of Sialic Acid 247 4.3. Recognition during Thrombosis 248

5. Platelet-Particle Interaction 250 5.1. Phagocytosis by Platelets 250 5.2. Platelets and Colloid Clearance 252

6. RES Uptake of Platelet Activators 253 7. Platelet-Macrophage Interactions 254

7.1. Immune Interactions 254 7.2. Role of Prostaglandins 255

xx CONTENTS

7.3. Role of Leukotrienes 256 7.4. Platelet-Activating Factor and Other Interactions 256

8. Summary and Conduding Statement 257 References 258

11. RES-Leukocyte Interactions

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

1. Introduction 267 2. Types of Interaction between RES Cells and Lymphocytes 267

270 3. Interaction of RES Cells and Nonlymphoid Leukocytes 4. Interaction of RES Cells and T Lymphocytes 271

4.1. Introduction 271 4.2. Proliferative Responses 4.3. T Helper Cells 273

272

4.4. Dendritic Cell-Lymphocyte Interaction 4.5. Development of the T Repertoire 275

273

4.6. Mechanisms of RES-T Lymphocyte Interaction 5. Interaction of RES Cells and B Lymphocytes 279 6. Lymphocyte Activation of RES Cells 280

6.1. Introduction 280 6.2. In Vivo Phenomena 280 6.3. In Vitro Interactions between Lymphocytes and

Macrophages 281 7. Condusion 283

References 284

276

III. ReguIatory Interactions with Blood Metabolites and Constituents

12. Glucose Regulation and the RES

}AMES P. FILKINS

1. Introduction 291 2. Glucoregulatory Alterations in Endotoxicosis 292

2.1. Phases of Blood Glucose Responses 292 2.2. Changes in Inputs and Outputs of the Glucose Pool 292 2.3. Insulin Changes in Endotoxicosis 293

CONTENTS xxi

3. Glucoregulatory Alterations after RES Perturbations 294 3.1. Changes in Inputs to the Glucose Pool 294 3.2. Changes in Outputs from the Glucose Pool 295 3.3. Insulin Changes 295

4. Glucoregulatory Monokines 296 4.1. Leukocytic Endogenous Mediator (LEM) 296 4.2. Glucocorticoid-Antagonizing Factor (GAF) 296 4.3. Macrophage Insulin-like Activity (MILA) 297 4.4. Macrophage Insulin-Releasing Activity (MIRA) 297

5. Glucose Regulation and RES Endocytic Functions 298 5.1. Intravascular Clearance Defects during Hypoglycemia 298 5.2. Unifying Schema 298

6. Concluding Remarks 300 References 300

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

1. Introduction 305 2. Interaction of Lipids with Free Macrophages 306

2.1. Artificial Lipid Substrates 306 2.2. Natural Lipid Substrates 307

3. Interaction of Lipids with Tissue Macrophages 309 3.1. Artificial Lipid Substrates 309 3.2. Natural Lipid Substrates 314

4. Perspectives in the Use of Macrophage Activity in the Prevention or Treatment of Atherosclerosis 325

References 326

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

MICHAEL C. POWANDA and EUZABETH D. MOYER

1. Introduction 331 2. Interactions of Specific Proteins with RES, Lymphocytes, and

Fibroblasts 332 2.1. a1-Antitrypsin 2.2. a2-Macroglobulin 2.3. C-Reactive Protein 2.4. Transferrin 338

332 334

336

2.5. Lipoproteins 339 2.6. Fibronectin 341

xxii CONTENTS

3. Summary and Conclusions 342 Referenees 344

15. Iron Metabolism

F ARID 1. HAURANI and SAMIR K. BALLAS

1. Introduction 353 2. Uptake of Iron Carriers by the RES 353

2.1. Haptoglobin and Hemopexin 353 2.2. Erythroeyte 355

3. Proeessing and Release of Iron from the RES 360 3.1. Coneepts and Meehanisms of Iron Release 360 3.2. Methods of Study of RES Activity in Relation to Iron 366 3.3. Factors That Deerease Iron Release 367 3.4. Factors That Inerease Iron Release 371

Referenees 372

16. Lead and Cadmium: Effect on Host Defense Mechanisms and Toxie Interactions with Bacterial Endotoxin

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

1. Relative Toxicity of Lead and Cadmium on Phagoeytes 380 2. Effeet of Lead and Cadmium on Phagoeytie Capacity 381

2.1. In Vitro Studies 381 2.2. Respiratory Exposure 381 2.3. Parenteral Administration 382 2.4. Oral Administration 385

3. Metabolie Effects of Lead and Cadmium on Phagoeytes 385 4. Effeet of Lead and Cadmium on Humoral and Cellular

Immunity 387 4.1. Humoral Immunity 387 4.2. Lymphoeyte Blast Cell Transformation 388 4.3. Cellular Immunity 388

5. Effeet of Lead and Cadmium on Suseeptibility to Infections 389 5.1. Bacterial Infeetions 389 5.2. Viral Infections 390 5.3. Parasitic Infeetions 390

6. Toxie Interactions of Lead and Cadmium with Bacterial Endotoxin 391

7. Conclusion 396 Referenees 396

Index 401

Contents of Volume 78

IV. Regulation and Macrophage Secretions

1. Endocrinelike Activities of the RES: An Overview

ROBERT N. MOORE and L.JOE BERRY

2. Regulation of Complement Synthesis in Mononuclear Phagocytes

ROBERT C. STRUNK and HARVEY R. COL TEN

3. The Synthesis of Arachidonic Acid Oxygenation Products by Macrophages

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

4. Lysosomal Hydrolases

MARCO BAGGIOLINI

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

SIAMON GORDON and R. ALAN B. EZEKOWITZ

6. Interferon and Macrophages

DAvID O. LucAs and LOIS B. EpSTEIN

V. Clinical Physiology of the RES

7. Leukocytic Endogenous Mediator in Nonspecific Host Defenses

ROGER H. MITCHELL and RALPH F. KAMPSCHMIDT

8. Evaluation of RES Clearances in Man

JOHN W. B. BRADFIELD

9. RES Function in Experimental and Human Liver Disease

HEINRICH LIEHR

XXIlI

xxiv CONTENTS OF VOLUME 7B

10. Regional Phagocytosis in Man

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

11. Inflammatory Cell Dynamics in Man

JOHN W. REBUCK

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

THOMAS M. SABA

VI. Integrative Functions of the RES

13. Physiology and Pathophysiology of the Pulmonary Macrophages

JOSEPH D. BRAIN

14. Temperature Regulation and Fever

HARRY A. BERNHEIM

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

BURTON M. ALTURA

16. Radiation Effects on Phagocytic Cells of the RES

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

17. Role of the Reticuloendothelial System in Shock

SHERWOOD M. REICHARD and ANDY C. REESE

18. Toxic Oxygen Products in Shock

SHERWOOD M. REICHARD

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

G. HORPACSY

Index