Mononuclear Phagocytes Characteristics, Physiology and Function

edited by

Ralph van Furth

Department of Infectious Diseases University Hospital Leiden, The Netherlands

1985 MARTINUS NIJHOFF PUBLISHERS ~. a member of the KLUWER ACADEMIC PUBLISHERS GROUP .11 DORDRECHT / BOSTON / LANCASTER .~

Distributors

jar the United States and Canada: Kluwer Academic Publishers, 190 Old Derby Street, Hingham, MA 02043, USA jar the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LAI lRN, UK jar all other countries: Kluwer Academic Publishers Group, Distribution Center, P.O. Box 322, 3300 AH Dordrecht, The Netherlands

Book information

ISBN-13: 978-94-010-8723-0

Library of Congress Cataloging in Publication Data

Main entry under title:

Mononuclear phagocytes.

Proceedings of the fourth Conference on Mononuclear Phagocytes, held in Leiden, May 9-16, 1984.

Includes index. 1. Macophages--Congresses. 2. Monocytes--Congresses.

I. Furth, Ralph van. II. Conference on Mononuclear Phagocytes (4th: 1984 : Leiden, Netherlands) QR185.8.M3M65 1985 616.07'9 85-7219 I SBN-13: 978-94-010-8723-0 e-I SBN-13: 978-94-009-5020-7 DOl: 10.1007/978-94-009-5020-7

Copyright

© 1985 by Martinus Nijhoff Publishers, Dordrecht. Softcover reprint of the hardcover 1st edition 1985

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publishers, Martinus Nijhoff Publishers, P.O. Box 163, 3300 AD Dordrecht, The Netherlands.

Contents

List of contributors v

Preface IX

Surface properties of mononuclear phagocytes

1. Differentiation antigens of mouse macrophages and polymorphonuclear leukocytes 3 S. Gordon, S. Hirsch, and P. Starkey

2. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80 9 D.A. Hume and S. Gordon Discussion 18

3. The expression of antigen F4/80 and Ia on peritoneal macrophages in normal and BeG immunized mice 19 E.e.M. Hoefsmit and R.H.l. Beelen Discussion 30

4. Human macrophage antigens 31 R.F. Todd III, A. Biondi, and l.A. Roach Discussion 40

5. Immunocytochemical studies of human mononuclear phagocytes and dendritic cells 41 M.D. Witmer and R.M. Steinman Discussion 48

6. Quantitative analysis of monoclonal antibody binding to individual mononuclear phagocytes 49 P.H. Nibbering, P.e.l. Leijh, and R. van Furth Discussion 58

7. The mannose receptor of macrophages: a current perspective 59 P.D. Stahl, T.E. Wileman, and V.L. Shepherd Discussion 66

8. Soluble and membrane bound murine immunoglobulin Fc receptor 67 E. Pure and l.e. Unkeless Discussion 74

9. Internalization and fate of macrophage Fc receptors during receptor-mediated endocytosis 75 I.S. Mellman and P. Ukkonen Discussion 84

10. Macrophage membranes and clathrin 87 l. Aggeler, R. Takemura, B.A. Nichols, and Z.A. Werb Discussion 98

VI

11. Heterogeneity of 5'-nucleotidase activity of wheat-germ agglutinin binding In mononuclear phagocytes 99 L.A. Ginsel, R. de Water, J.W.M. van der Meer, and W.Th. Daems Discussion 113

12. Inherited LFA-l, Mac-l deficiency and its molecular biology 115 T.A. Springer, L. Sastre, F. Schmalstieg, and D. Anderson Discussion 123

13. Bone marrow stromal cells - fibroblasts and macrophages 125 D.F. Bainton Discussion 136

Interactions of complement with membranes of mononuclear phagocytes

14. The role of complement in macrophage functions 139 M.R. Daha

15. Tissue and species specific regulation of complement biosynthesis in mononuclear phagocytes 147 H.R. Colten, F.S. Cole, R. Sackstein, and H.S. Auerbach Discussion 155

16. Regulation of expression and cell surface motility of the C3b receptor on neutrophils and monocytes 157 D.T. Fearon and R.M. Jack Discussion 162

17. Parameters of the stimulation of human monocytes by factor B of the complement system 163 H. Baumgarten, M. Opperman, M. Schulze, and O. Gotze Discussion 171

18. Uptake and degradation of the Clq subcomponent of complement by adherent guinea pig peritoneal macrophages 173 M.R. Daha, R. Veerhuis, and L.A. van Es Discussion 180

19. Regulation of the function of receptors for C3b and C3bi on human mononuclear phagocytes by receptors for other ligands 183 S.D. Wright and S.c. Silverstein Discussion 191

20. Role of macrophage-complement receptors and macrophage complement uptake of zymosan 193 R.A.B. Ezekowitz, R.B. Sim, and S. Gordon Discussion 198

In vivo kinetics and in vitro growth of mononuclear phagocytes

21. New perspectives on the kinetics of mononuclear phagocytes R. van Furth, M.M.C. Diesselhoff-den Dulk, W. Sluiter, and J.T. van Dissel Discussion

22. The origins and turnover kinetics of limbocytes C. W. Pugh and G. G. MacPherson Discussion

23. Origin of osteoclasts from bone marrow mononuclear phagocytes

201

209 211

220 221

VII

E.H. Burger, J.W.M. van der Meer, F.P. van de Wijngaert, and R. van Furth Discussion 231

24. Mononuclear phagocyte progenitors and growth factors 233 L.J. Guilbert Discussion 242

25. Proliferation and differentiation of mononuclear phagocytes in vitro 243 J.W.M. van der Meer, J.S. van de Gevel, R. de Water, L.A. Ginsel, C.H. Wouters, W.Th. Daems, and R. van Furth Discussion

26. Clonal analysis of bone marrow and macrophage cultures c.c. Stewart, E.B. Walker, C. Johnston, and R. Little Discussion

Secretion of products by mononuclear phagocytes

254 255

266

27. Control of apolipoprotein E secretion by macrophages 269 Z. Werb , J.R. Chin, R. Takemura, S.M. Frisch, R.L. Oropeza, and D.F. Bainton Discussion 278

28. The secretion of lipoprotein lipase by mononuclear phagocytes 279 E.M. Mahoney, J.C. Khoo, J.L. Witztum, and D. Steinberg Discussion 285

29. Autoregulatory effects of interleukin 1 on human monocytes 287 J.J. Oppenheim, K. Onozaki, and K. Matsushima Discussion 293

30. Macrophage elastase: regulatory concequences of the proteolysis of non-elastin tissue substrates 295 M.J. Banda, E.J. Clark, and Z. Werb Discussion 301

31. Determinants of generation and structural heterogeneity of fibroblast-activating principles of human mononuclear phagocytes 303 J.G. Dohlman and W.J. Goetzl Discussion 309

32. Signal-response coupling in the arachidonic acid cascade of macrophages 311 A.A. Aderem, W.A. Scott, and Z.A. Cohn Discussion 318

33. Influence of macrophage products on enzyme and prostglandin E2 release by chondrocytes 319 J. Schnyder, V. Evequoz, U. Trechsel, and M. Baggiolini Discussion 326

Mobilization and chemotaxis of mononuclear phagocytes

34. Macrophage movements J.H. Hartwig and T.P. Stossel Discussion

35. Gelsolin: a calcium-modulated actin fragmenting protein in cytoplasm and plasma H.L. Yin and T.P. Stossel Discussion

329

336 337

342

VIII

36. Stimulus-response coupling of a chemoattractant receptor on mononuclear phagocytes R. Snyderman

37. Mathematical analysis of the macrophage response to bacterial challenge in the lung D.A. Lauffenburger Discussion

Membrane electrophysiology of mononuclear phagocytes

38. Introduction to the membrane electrophysiology of mononuclear phagocytes C. Ince

39. Membrane hyperpolarization and ionic channels in cultured human monocytes C. Ince and D.L. Ypey

343

351

358

361

369

Discussion 378 40. Evidence for both a calcium-activated potassium conductance and an inward rectifying potassium

conductance in macrophages 379 E.K. Gallin and P.A. Sheehy Discussion 387

41. Potassium channels and conductance in cultured mouse peritoneal macrophages 389 D.L. Ypey, D.E. Clapham, and C. Ince Discussion 397

42. Nature of transmembrane signal associated with binding to the macrophage IgG Fe receptor 399 J.D-E. Young and Z.A. Cohn Discussion

Intra- and extracellular cytotoxicity of mononuclear phagocytes

43. Regulation of macrophage oxidative metabolism and antiparasitic activity C.F. Nathan

407

411

Discussion 421 44. Characterization of phagocyte NADPH oxidase 423

R. Rossi, P. Bellavite, M.C. Serra, and E. Papini Discussion 433

45. Role of t~e plasma membrane in the regulation of superoxide anion release by macrophages 435 G. Berton and S. Gordon Discussion 444

46. Enhancement of the oxidative metabolic response of macrophages by proteolytic enzymes 445 R.B. Johnston, Jr., M.J. Pabst, Ch.P. Speer, H.B. Hedegaard, R.F. Rest, and S.M. Bryant Discussion 451

47. Somatic hybridization of monocytes: a method to study the genetic heterogeneity of chronic gralunomatous disease and the molecular composition of the phagocyte oxidase system 453 D. Roos, M. de Boers, R.S. Weening, and M.N. Hamers Discussion 461

48. Membrane stimulation and intracellular killing of micro-organisms by human monocytes 463 P.c.J. Leijh, M.Th. van den Barselaar, Th.L. van Zwet, L.A. Ginsel, and R. van Furth Discussion 471

49. Influence of monocytes on the antibacterial activity of penicillin G on Staphylococcus aureus 473

IX

P.J. van den Broek and R. van Furth Discussion 477

50. Effects of nitrogenous bases on macrophage lysosomal movements and phagosome-lysosome fusion 479 P. D'Arcy Hart and M.R. Young Discussion 485

51. Properties of resident and inflammatory macrophages in mouse liver 487 D.A. Lepay, R.M. Steinman, C.F. Nathan, H.W. Murray, and Z.A. Cohn Discussion 491

52. Tumor cell recognition and destruction by activated macrophages: effector and regulatory mecha-nisms 493 D.O. Adams and T.A. Hamilton Discussion 501

Lymphokines and T -lymphocyte activation of mononuclear phagocytes

53. Dendritic cell-initiated T lymphocyte activation J.M. Austyn, D.E. Weinstein, A. Granelli-Piperno, and R.M. Steinman Discussion

54. Modulation of macrophage plasma membrane antigens and receptors by activation R.A.B. Ezekowitz, M. Hill, and S. Gordon Discussion

55. Molecular characterization of macrophage activating factor for tumor cytotoxicity R.D. Schreiber

505

511 513

521 523

Discussion 531 56. The role of T cell clone- and hybridoma-derived lymphokines in macrophage activation 533

P.H. Krammer, B. Echtenachter, U. Hamann, B. Kaltmann, U. Kees, C. Kubelka, and D. Gemsa Discussion 540

57. Role of T lymphocyte clones in cell-mediated immunity 541 S.H.E. Kaufmann, V. Brinkmann, A.F. Kiderlen, M.-L. Lohmann-Matthes, I. Miiller, and L.J. Wrazel Discussion 551

58. Role of T lymphocytes during murine BCG infections 553 G. Milon, P. Goossens, and G. Marchal Discussion 560

59. Role of T lymphocytes in granuloma formation 561 H. Niiher, U. Sperling, and H. Hahn Discussion 569

60. Refractory response of mouse lung macrophages to lipopolysaccharide 571 T. Tokunaga and K.S. Akagawa Discussion 581

61. Induction of phenotypic alterations in macrophages by migration inhibitory factors 583 C. Sorg, E. Michels, U. Malorny, and J. Knop Discussion 590

x

Macrophages and intracellular pathogens

62. Interaction of schistosomes and macrophages J.P. Dessaint, A. Capron, C. Auriault, and M. Joseph Discussion

63. Interaction of macrophages and intra-erythrocytic malaria parasites H.L. Shear Discussion

64. The endocytic system of Leishmania-infected macrophages M. Rabinovitch Discussion

65. Interactions between human mononuclear phagocytes and Legionella pneumophila M.A. Horwitz Discussion

66. Cell mediated immunity in lepromatous and tuberculoid leprosy G. Kaplan and Z.A. Cohn Discussion

Genetic control of the kinetics and functions of mononuclear phagocytes

67. Genetic control of macrophage response to infection E. Skamene and M.M. Stevenson

593

599 601

609 611

620 621

629 631

642

647

Discussion 654 68. Genetic control of the humoral regulation of monocytopoiesis 655

W. Sluiter, I. Elzenga-Claasen, A. van der Voort van der Kley-van Andel, and R. van Furth Discussion 665

69. Differences in intracellular killing of Salmonella typhimurium by macrophages of inbred mouse strains 667 J.T. van Dissel, P.C.J. Leijh, and R. van Furth Discussion 676

70. The role of the macrophage in genetically controlled resistance and susceptibility to leishmaniasis 677 J.M. Blackwell, R.P. Crocker, and J.Y. Channon Discussion 684

Coagulation, vasculature, and mononuclear phagocytes

71. Cellular pathways and signals for the indlU(tion of biosynthesis of initiators of the coagulation protease cascade by cells of the monocyte lineage 687 T.S. Edgington, H. Helin, S.A. Gregory, G. Levy, D.S. Fair, and B.S. Schwartz Discussion 697

72. Formation of blood coagulation factors by mononuclear phagocytes 699 B. 0sterud, U. Lindahl, R. Seljelid, J. B0gwald, and S.O.Kolset

73. The generalized Shwartzman reaction: effects of a glucocorticosteroid and endotoxin on thrombo-plastin synthesis by monocytes 705 B. 0sterud, J.O. Olsen, and A. Tindall Discussion 711

XI

74. Macrophage procoagulants and microvascular permeability: roles in the extravascular coagulation of cellular immunity 713 J. Carr, L. VanDeWater, D. Senger, A.M. Dvorak, and H.F. Dvorak Discussion 721

75. Monocyte receptors for fibronectin 723 B. Hosein, M.W. Mosesson, and C. Bianco Discussion 731

76. Human monocyte interaction with platelets and endothelial cells: synthesis of arachidonic acid metabolites 733 N.A. Pawlowski, W.A. Scott, and Z.A. Cohn Discussion 746

77. Effects of mononuclear phagocytes and their secretory products on vascular endothelium 747 M.P. Bevilacqua, J.S. Pober, R.S. Cotran, and M.A. Gimbrone, Jr. Discussion 753

78. Interactions between leukocytes and endothelial cells in vitro 755 M.B. Furie and S.C. Silverstein Discussion 763

79. Regulation of angiogenesis by macrophages 765 M.J. Banda, D.R. Knighton, J.A. Jensen, TK. Hunt, and Z. Werb Discussion 774

Macrophages in experimental pathology

80. Oxidant and protease effectors in acute inflammation 777 C.G. Cochrane, R.G. Spragg, 1.U. Schraufstatter, S.D. Revak, P.A. Hyslop, and D.B. Hinshaw Discussion 784

81. Glomerular injury: functional and phenotypic characteristics of resident and infiltrating macro-phages 785 G.F. Schreiner, E.R. Unanue, and R.S. Cotran Discussion 793

82. The role of the mononuclear phagocytes in primate and rabbit models of atherosclerosis 795 M.E. Rosenfeld, A. Faggiotto, and R. Ross Discussion 802

83. Macrophage lipoprotein metabolism in atherosclerosis 803 A.M. Fogelman, B.J. Van Lenten, M. Hokom, J. Seager, H. Wong, M. Navab, S. Shapiro, M.E. Haberland, and P.A. Edwards Discussion 810

84. Role of monocytes in infective endocarditis 811 J. Thompson, M.J.M. Meddens, L. ThOrig, and R. van Furth Discussion 817

Summation

85. Visions of the future? 821 Z.A. Cohn

Index 825

List of contributors

D.O. Adams Dept. of Pathology Duke University Medical Center P.O. Box 3712 Durham, North Carolina 27710 USA

A.A. Aderem The Rockefeller University 1230 York Avenue New York, NY 10021 USA

J. Aggeler Laboratory of Radiobiology and Environmental Health University of California San Francisco, California 94143 USA

J.M. Austyn Nuffield Department of Surgery John Radcliffe Hospital Headington, Oxford OX3 9DU United Kingdom

M. Baggiolini Theodor Kocher Institute Freiestrasse 1 Ch-30l2 Berne Switzerland

D.F. Bainton University of California School of Medicine Dept. of Pathology San Francisco, California 94143 USA

M.J. Banda Laboratory of Radiobiology and Environmental Health University of California San Francisco, CA 94143 USA

H. Baumgarten Zentrum fUr Hygiene und Humangenetik U niversitiitsklinik G6ttingen Abt. fUr Immunologic Kreuzbergring 57 D-3400 G6ttingen W. Germany

G. Berton Istituto di Patologia Generale Universita di Verona Verona Italy

M.P. Bevilacqua Harvard Medical School Brigham Women's Hospital Dept. of Pathology 75 Francis Street Boston, Ma 02115 USA

C. Bianco The Greater New York Blood Program Research and Development The New York Blood Center American Red Cross 310 East 67 Street New York, NY 10021 USA

J.M. Blackwell London School of Hygiene and Tropical Medicine Keppel Street ( Gower Street) London WClE 7HT England

P. Brakman Gaubius Institute TNO Herenstraat Sid 2313 AD Leiden The Netherlands

XIV

P.J. van den Broek Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden Thc Netherlands

E.1I. Burger Schools of Dentistry and Medicine Dept. of Histology Free University De Boelelaan 1115 1081 HV Amsterdam The Netherlands

J. Carr Harvard Medical School Dept. of Pathology Beth Israel Hospital Boston, Mass. 02215 USA

e.G. Cochrane Dept. of Immunology Scripps Clinic and Research Foundation 10666 North Torrey Pines Road La Jolla, Ca 92037 USA

Z.A. Cohn The Rockefeller University 1230 York Avenue New York, NY 10021 USA

H.R. Colten Harvard Medical School, CHMN Dept. of Pediatrics Division of Cell Biology 300 Longwood Avenue Boston, Ma 02115

USA

W.Th. Daems University of Leiden Lab. for Electron Microscopy Rijnsburgerweg 10 2333 AA Leiden The Netherlands

M.R. Daha Dept. of Nephrology University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

P. D'Arcy Hart National Institute for Medical Research The Ridgeway, Mill Hill London, NW71AA England

P. Davies Dept. of Immunology & Inflammation Merck Institute for Therapeutic Research P.O. Box 2000 Rahway, NJ 07065 USA

J. P. Dessaint Institut Pasteur Centre d'Immunologie et de Biologie Parasitaire 15, Rue Camille Guerin 59019 Lille Cedex France

J.T. van Dissel Dept. of Infectious Diseases Academisch Ziekenhuis Rijnsburgerweg 10 2333 AA Leiden The Netherlands

J.G. Dohlman University of California School of Medicine Division of Allergy and Immunology San Francisco, Ca 94143 USA

H.F. Dvorak Harvard Medical School Dept. of Pathology Beth Israel Hospital Boston, Mass. 02215 USA

T.S. Edgington Research Institute of Scripps Clinic

Program in Immunology and Pathobiology of Neoplasia 10666 North Torrey Pines Road La Jolla, Ca. 92037 USA

R.A.B. Ezekowitz The Children's Hospital 300 Longwood Avenue Boston, Mass. 02115 USA

D.T. Fearon Harvard Medical School

Brigham and Women's Hospital The Seeley G. Mudd Building 250 Longwood Avenue Boston, Ma. 02115 USA

A.M. Fogelman Division of Cardiology UCLA School of Medicine Los Angeles, California 90024 USA

R. van Furth Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

E.K. Gallin Dept. of Physiology Armed Forces Radiobiology Research Institute Bethesda, Maryland 20814 USA

J.I. Gallin National Institute of Allergy and Infectious Diseases Laboratory of Clinical Investigation National Institutes of Health Building 10, Room 11N114 Bethesda, Maryland 20205 USA

M.A. Gimbrone lr. Harvard Medical School Brigham Women's Hospital Dept. of Pathology 75 Francis Street Boston, Ma 02115 USA

L.A. Ginsel University of Leiden Lab. for Electron Microscopy Rijnsburgerweg 10 2333 AA Leiden The Netherlands

E.]. Goetzl University of California School of Medicine Division of Allergy and Immunology San Francisco, Ca. 94143 USA

S. Gordon Sir William Dunn School of Pathology University of Oxford South Parks Road Oxford OX13RE England

O. Gotze Zentrum fUr Hygiene und Humangenetik U niversitatsklinik Gottingen Abt. fUr Immunologie Kreuzbergring 57 D-3400 Gottingen W. Germany

L.J. Guilbert University of Alberta Dept. of Immunology 845 E Medical Sciences BId. Edmonton, Alberta T6G 2H7, Canada

H. Hahn Institut fUr Medizinische Mikrobiologie der Freien Univcrsitat Berlin Hindenburgdamm 27 1000 Berlin 45 W. Germany

1.H. Hartwig Harvard Medical School Massachusetts General Hospital Hematology-Oncology Unit Cox Building, 6th Floor Boston, Mass. 02114 USA

E.C.M. Hoefsmit Dept. Electron Microscopy Medical Faculty Free University P.O. Box 7161 1007 MC Amsterdam The Netherlands

M.A. Horwitz Dept. of Cellular Physiology The Rockefeller University 1230 York Avenue New York, 10021 USA

B. Hosein The Greater New York Blood Program Research and Development The New York Blood Center

xv

XVI

American Red Cross 310 East 67 Street New York, NY 10021 USA

D.A. Hume Dept. of Medicine and Clinical Science Australian National University 4th Floor, Central Health Laboratory Building Woden Valley Hospital Garran, ACT 2606 Australia

C. Ince Dept. of Fysiology University of Leiden Wassenaarseweg 62 2333 AL Leiden The Netherlands

R.B. Johnston Jr. National Jewish Hospital and Research Center National Asthma Center Dept. of Pediatrics 3800 East Colfax A venue Denver, Colorado 80206 USA

G. Kaplan The Rockefeller University 1230 Y ork Avenue New York, NY 10021 USA

S.H.E. Kaufmann Max-Planck-Institut fUr Immunobiologie Postfach 1169 0-7800 Freiburg-Zahringen W. Germany

P.H. Krammer Institut fiir Immunologie und Genetik Deutsches Krebsforschungszentrum 1m Neuenheimer Feld 280 0-6900 Heidelberg W. Germany

H.L. Langevoort Free University Dept. of Histology Medical Faculty Van der Boechorststraat 7 1081 BT Amsterdam The Netherlands

D.A. Lauffenburger

University of Pennsylvania Dept. of Chemical Engineering Towne Building 03 220 S. 33rd Street Philadephia, Pennsylvania 19104 USA

D. Lepay The Rockefeller University 1230 York A venue New York, NY 10021 USA

P.c.J. Leijh Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

G.G. MacPherson Sir William Dunn School of Pathology University of Oxford South Park Road Oxford OX1 3RE England

E.M. Mahoney E.R. Squibb & Sons, Inc. The Squibb Institute for Medical Research P.O. Box 4000 Princeton, New Jersey 08540 USA

P.L. Meenhorst Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

J.W.M. van der Meer Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

I. Mellman Yale University School of Medicine Dept. of Cell Biology 333 Cedar Street P.O. Box 3333 New Haven, Connecticut 06510 USA

G. Milan Institut Pasteur 28, Rue du Dr. Raux 75724 Paris Cedex 15 France

H. Niiher Institut fUr Medizinische Mikrobiologie der Freien Universitat Berlin Hindenburgdamm 27 1000 Berlin 45 W. Germany

C. Nathan The Rockefeller University 1230 York A venue New York, NY 10021 USA

P.H. Nibbering Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

V. Nussenzweig New York University Medical Center School of Medicine Dept. of Pathology 550 First Avenue New York, NY 10016 USA

J.J. Oppenheim Laboratory of Molecular Immunoregulation National Cancer Institute Frederick Cancer Research Facility Building 560, Room 31-71 Frederick, Maryland 21701 USA

B. 0s1erud Institute of Medical Biology University of Tromso 9001 Tromso Norway

N.A. Pawlowski The Rockefeller University Laboratory of Cellular Physiology and Immunology 1230 York A venue New York, NY 10021 USA

C.W. Pugh Sir William Dunn School of Pathology University of Oxford South Park Road Oxford OXI 3RE England

E. Pure The Rockefeller University 1230 York A venue New York, NY 10021 USA

M. Rabinovitch New York University Medical Center School of Medicine Dept. of Cell Biology 550 First Avenue New York, NY 10016 USA

D. Roos Centraal Laboratorium van de Bloedtransfusiedienst Plesmanlaan 125 1066 CX Amsterdam The Netherlands

M. Rosenfeld University of Washington School of Medicine Dept. of Pathology C514 Health Sciences, SM-30 Seattle, WA 98195 USA

F. Rossi Istituto di Patologia Generale Facolta di Medicina e Chirurgia Universita degli Studi di Verona Strada Ie Grazie 37134 Verona Italia

J. Schnyder Wander Ltd. P.O. Box 2747 CH-3001 Berne Switzerland

R.D. Schreiber Scripps Clinic and Research Foundation Dept. of Immunology 10666 North Torrey Pines Road La Jolla, Ca 92037 USA

XVII

XVIII

G.F. Schreiner Harvard Medical School Brigham Women's Hospital Dept. of Pathology 75 Francis Street Boston, Ma 02115 USA

W.A. Scott The Squibb Institute for Medical Research P.O. Box 4000 Princeton, NJ 08540 USA

H.L. Shear New York University Medical Center School of Medicine Division of Parasitology Dept. of Microbiology 550 First Avenue New York, NY 10016 USA

S. C. Silverstein The Rockefeller University 1230 Y ork Avenue New York, NY 10021 USA

E. Skamene Division of Clinical Immunology and Allergy 1650 Cedar Avenue Montreal, Que. H3G, lA4, Canada

W. Sluiter Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

R. Snyderman Duke University Medical Center Division of Rheumatic and Genetic Diseases Dept. of Medicine P.O. Box 3892 Durham, North Carolina 27710 USA

C. Sorg Hautklinik der Westfiilische Wilhelms-Universitiit Von-Esmarch-Strasse 56 D-4400 Munster W. Germany

T.A. Springer Harvard Medical School Dana-Farber Cancer Institute Lab. of Membrane Immunochemistry 44 Binney Street Boston, Mass. 02115 USA

P.D. Stahl Washington University School of Medicine Dept. of Physiology and Biophysics 660 South Euclid Avenue St. Louis, Miss. 63110 USA

R.M. Steinman The Rockefeller University 1230 York Avenue New York, NY 10021 USA

c. C. Stewart Los Alamos National Laboratory Experimental Pathology P.O. Box 1663 Los Alamos, New Mexico 87545 USA

J. Thompson Dept. of Infectious Diseases University Hospital Rijnsburgerweg 10 2333 AA Leiden The Netherlands

R.F. Todd Simpson Memorial Research Institute Dept. of Internal Medicine The University of Michigan Ann Arbor, Michigan 48109 USA

T. Tokunaga National Institute of Health Dept. of Cellular Immunology 2-10-35, Kamiosaki, Shinagawaku Tokyo Japan

z. Werb University of California Laboratory of Radiobiology and Environmental Health San Francisco, California 94143 USA

D.M. Witmer The Rockefeller University 1230 York Avenue New York, NY 10021 USA

S.D. Wright The Rockefeller University 1230 York Avenue New York, NY 10021 USA

H.L. Yin Harvard Medical School Massachusetts General Hospital Hematology Oncology Unit

Cox Building, 6th Floor Boston, Mass. 02114 USA

1.D.E. Young The Rockefeller University 1230 York Avenue New York, NY 10021 USA

D.L. Ypey Dept. of Physiology University of Leiden Wassenaarseweg 62 2333 AL Leiden The Netherlands

XIX

Preface

Sixteen years have passed since the first Leiden Conference on Mononuclear Phagocytes. That first meeting led to new nomenclature, i.e., the Mononuclear Phagocytes System (MPS), which was published in the Bulletin of the World Health Organization (R. van Furth, et aI., Bull. WHO, 1972, 46: 845-852). The paradigm of the MPS has the advantage of being much more consistent than the Reticuloendothelial System (RES) (L. Aschoff, Ergebn. Inn. Med. Kinderheilk. 1924, 26:1), because cells with similar characteristics can be classified in the same category.

The essence ota new concept is, according to Popper, that it must be susceptible to falsification. This has been attempted several times for the MPS by those who adhere to the RES. However, in biology no one can be certain of truth. Any theory must be based on experimental observations and/or theoretical consider­ations and both should be presented in such a way that others can try to refute it, then or later. One may have a theoretical or a pragmatic preference for a theory which at a given time is regarded as possibly truc, but later it may be shown to be false. In other words, what we present in this volume is regarded as true at this moment, but others may consider it as not true and try to disprove it. Controversies often stimulate new research. One of the fundamental qualities of a meeting such as this is openness and the willingness to discuss the results, to formulate a more general concept on the basis of experimental results, and to listen to those who disagree.

The concept of the MPS has stimulated much research in the area of the physiology and pathology of mononuclear phagocytes. At present, this term is found in many modern textbooks in such fields as histology, pathology, internal medicine, and haematology, published in many languages.

The mononuclear phagocyte cell line originates in the bone marrow, where the dividing cells, monoblasts and promonocytes, reside and monocytes are formed. The monocytes leave the bone marrow and are transported by the peripheral blood to the body's organs and cavities, where they differentiate into macrophages. Thus, mononuclear phagocytes can differentiate into mature cells, and macrophages also can be activated by a number of stimuli, for example lymphokines formed by T lymphocytes. The differentiation and activation of mononuclear phagocytes is expressed in morphological and functional characteristics. Thesc processes are symbolized by the print reproduced on the cover, called Metamorphosis, by M.e. Escher.

The second Leiden Conference, which dealt with Mononuclear Phagocytes in Immunity, Infection and Pathology, was held in 1973. The proceedings of these first two conferences were published by Blackwell Scientific Publications, Oxford, London, Edinburgh, Melbourne. The third conference, which was con­cerned with the functional aspects of mononuclear phagocytes, was held in 1978 and its proceedings were published by Martinus Nijhoff Publishers, The Hague, Boston, London.

The fourth Leiden Conference (May 9-16,1984) dealt with the characteristics, physiology, and functions of mononuclear phagocytes and was organized by Z.A. Cohn, R. van Furth, and S. Gordon. This conference included such topics as the surface properties of cells, mobilization, in vivo kinetics, in vitro growth, chemotaxis, membrane electrophysiology, secretion and secretory products, complement-cell membrane

XXII

interactions, intracellular killing, extracellular cytotoxicity, lymphokine activation of macrophages, the role of macrophages in coagulation, genetic control of cell kinetics and functions, and the interaction between monocytes and endothelial cells. These subjects are discussed in the present volume, whose contents reflect the enormous strides made in research on mononuclear phagocytes during the last sixteen years.

Financial support for the Fourth Leiden Conference on Mononuclear Phagocytes was received from the Amsterdam-Rotterdam Bank NY, Bayer AG, Beecham Farma BY, Behringwerke AG, Ciba-Geigy BY, Eli Lilly Nederland, Gist Brocades Farmaca, ICI-Farma, Immuno AG, Institut Merieux, Lederle Nederland BY, Merck & Co. Inc., Merck Sharp & Dohme BY, Nederlandsche Middenstandsbank NY, Organon International BY, Pfizer Europe, Rhone-Poulenc Nederland BY, Roussel UCLAF, Sandoz Ltd., Squibb BY, Upjohn Nederland, the Wellcome Trust, and Zeiss Nederland BY, as well as from the Jo Keur Stichting, Leids Universiteits-Fonds, Nederlandse Yereniging voor Reumabestrijding, Nierstichting Neder­land, Dr. Saal van Zwanenbergstichting, and the Leiden University Hospital.

Special mention must also be made of the secretarial and other staff members, who contributed so much to the success of this six-day conference. In the preparation of this volume for publication the editor was assisted by Mrs Nettie Kaat.

R. van Furth