MACROPHAGESAND NATURAL KILLER CELLS Regulation and Function ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo NICHOLAS R. DI LUZIO, Tulane University School of Medicine EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, Rockland Research Institute RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 147 INTRAOVA RIAN CONTROL MECHANISMS Edited by Cornelia P. Channing and Sheldon J. Segal Volume 148 STRUCTURE AND FUNCTION RELATIONSHIPS IN BIOCHEMICAL SYSTEMS Edited by Francesco Bossa, Emilia Chiancone, Alessandro Ilinazzi-Agro, and Roberto Strom Volume 149 IN VIVO IMMUNOLOGY: Histophysiology of the Lymphoid System Edited by Paul Nieuwenhuis, A. A. van den Broek, and M. G. Hanna, Jr. Volume 150 IMMUNOBIOLOGY OF PROTEINS AND PEPTIDES-II Edited by M. Z. Atassi Volume 151 REGULATION OF PHOSPHATE AND MINERAL METABOLISM Edited by Shaul G. Massry, Joseph M. Letteri, and Eberhard Ritz Volume 152 NEW VISTAS IN GLYCOLIPID RESEARCH Edited by Akira Makita, Shizuo Handa, Tamotsu Taketomi, and Yoshitaka Nagai Volume 153 UREA CYCLE DISEASES Edited by A. Lowenthal A. Mori, and B. Marescau Volume 154 GENETIC ANALYSIS OF THE X CHROMOSOME: Studies of Duchenne Muscular Dystrophy and Related Disorders Edited by Henry F. Epstein and Stewart Wolf Volume 155 MACRO PHAGES AND NATURAL KILLER CELLS: Regulation and Function Edited by Sigurd J. Normann and Ernst Sorkin MACROPHAGES AND NATURAL KILLER CELLS Regulation and Function Edited by Sigurd J. Normann College of Medicine University of Florida Gainesville, Florida and Ernst Sorkin Department of Medicine Swiss Research Institute Davos, Switzerland PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data International RES Congress on Macrophages and Natural Killer Cells (9th: 1982: Davos, Switzerland) Macrophages and natural killer cells. (Advances in experimental medicine and biology; v. 155) Includes bibliographical references and indexes. 1. Macrophages - Congresses. 2. Phagocytes - Congresses. I. Normann, S. J. II. Sorkin, Ernst, 1920- . III. Series. [DNLM: 1. Killer cells-Physiology-Con gresses. 2. Macrophages-Physiology-Congresses. WI AD559 v. 155/WH 650 M1744 1982] QRI85.8.M3I57 1982 616.0719 82-16158 ISBN 978-1-4684-4396-7 ISBN 978-1-4684-4394-3 (eBook) DOl 10.1007/978-1-4684-4394-3 Proceedings of the Ninth International RES (Reticuloendothelial Society) Congress, held February 7 -12,1982, in Davos, Switzerland ©1982 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1982 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 TO ELIE METCHNIKOFF ON THE lOOTH ANNIVERSARY OF HIS DISCOVERY OF MACROPHAGES PREFACE This book is the outcome of a meeting held in Davos, Switzerland, February 7-12, 1982 focused primarily on mononuclear phagocytes and on natural killer (NK) cells. This IX International RES Congress was attended by 489 scientists from 31 countries and there were 340 scientific presentations in oral or poster session. The essential purpose of the Congress was to bring together scientists representing various aspects of mononuclear phagocyte biology to review and examine cri~ically the effects and mechanisms of macrophage growth control as well as the participatio~ of these cells in the afferent and efferent limbs of the immune response. Additional topics included the production and distribution of mono nuclear phagocytes; the intrinsic and extrinsic regulation of these cells; and the origin, nature, function and regulation of NK cells. The ultimate goal of the Congress was to enhance communication between scientists in various countries and disciplines so that new research directives could be defined with which to explore basic aspects of macrophage and NK cell participation in the control of cancer and infection. The macrophage is recelvlng increased scientific attention which is a proper reflection of the central role this cell plays in homeo stasis. The Congress was designed to emphasize the following unique and timely aspects of macrophage biology: (a) The various growth regulating aspects of macrophages were examined with respect to both normal and abnormal cellular proliferation. Discussion focused upon the regulatory role of macrophages in hematopoiesis and lymphocytic and fibroblastic proliferation as examples of normal cell processes, and these effects were contrasted with those on neoplastic and trans formed cells. (b) Regulation of macrophage function by prostaglan dins, complement, and interferon was analyzed from the point of view of an auto-regulatory network. (c) The parallel between chemotaxis and phagocytosis was explored with reference to recognition events and cytoskeletal function. (d) The role of macrophages in the af- vil PREFACE ferent and efferent limbs of the immune response focused on the nature of lymphocyte-macrophage communication and the role of I region as- sociated determinants. ' This focus on macrophages and homeostasis generated certain questions which formed the basis of the Congress and which are ad dressed in the papers collected in this volume. Among the questions are the following: By what means does the macrophage plasma membrane recognize for eigness? Is chemotaxis a form of directional phagocytosis? How are trans-membrane signals utilized to effect microfilament and microtubular functions essential to chemotaxis and phagocytosis? Can monoclonal antibodies or physical properties be used to define or isolate subsets of macrophages with restricted activities? Do all macrophages have the capacity to express Ia antigens despite the fact that only a minority of the cells express the product of the Ir gene at any given time? How do lymphokines activate macrophages? Is a cell which produces colony stimulating factor capable of respond ing to lymphokine and becoming cytotoxic to tumor cells? Do monokines and NK cells act as suppressor cells to certain lympho cyte functions? Are the prostaglandins and colony stimulating factors that participate in hematopoiesis also stimulating or retarding growth of transformed cells? It is becoming increasingly evident that NK cells and macrophages share the common property of non-specific cytotoxic and bactericidal activities. Although the spectrum of susceptible target cells may differ and the two cells may be derived from different cell lineages, it appeared appropriate to include in the Congress and in this volume a discussion of natural resistance mechanisms. Spontaneously occurring cytotoxic cells may influence cancer emergence and hematopoietic differentiation as well as graft rejection and viral infection. The activity of these cells is modulated by interferon and other agents which also activate macrophages. In the discussion oriented symposium which concluded the Congress and which is reproduced here, the critical issues were addressed of whether or not the cells responsible for natural resistance to grafts of renal, hematopoietic and leukemic cells, to carcinoma, sarcoma and melanoma cells and to certain viruses are related and which kinds of molecules are recognized on the surface of neoplastic and non-neoplastic tar- PREFACE gets. In addition, the nature of surface markers on effector cells and the regulation of natural resistance mechanisms were presented, including the interaction of effector and regulatory accessory cells. We hope that this volume reproduces the essence of the scientific exchange that characterized the IX International RES Congress. S. Normann Gainesville, Florida, USA E. Sorkin Davos, Switzerland ACKNOWLEDGEMENTS IX INTERNATIONAL RES CONGRESS SPONSORING SCIENTIFIC ORGANIZATIONS American Reticuloendothelial Society European Reticuloendothelial Society Japanese Reticuloendothelial Society Swiss Society of Allergology and Immunology CONTRIBUTORS Registration fees rarely cover ~he costs of a meeting and gener ally arrive late after certain expenses have been incurred. Thus, the financial health of the Congress would not have been possible with out the timely and generous support of our friends in industry, gov ernment, -and private foundations. We express sincere gratitude for the financial support provided by the following: Accurate Chemical & Scientific Corp., Westbury, NY Bayer AG, Leverkusen, Germany Centre de Recherche Merrell International, Strasbourg, France Ciba-Geigy AG, Basel, Switzerland Eli Lilly and Company, Surrey, England Gruppo Lepetit, Milano, Italy Hoffmann-La Roche AG, Basel, Switzerland Imperial Chemical Ind. Ltd., Macclesfield, Cheshire, U.K. xii ACKNOWLEDGEMENTS Merck Sharp & Dohme, Rahway, NJ, USA Monsanto Co., St. Louis, MO, USA Nestle S.A., Vevey, Switzerland Nyegaard Cie., Oslo, Norway Sandoz AG, Basel, Switzerland Solco AG, Basel, Switzerland Schweizerische Kreditanstalt, Davos, Switzerland Swiss Cancer League, Berne, Switzerland Swiss National Science Foundation, Berne, Switzerland Swissair, Zurich, Switzerland The American Reticuloendothelial Society The European Reticuloendothelial Society The Japanese Reticuloendothelial Society Upjohn, Kalamazoo, MI, USA US Pharmaceutical Corp., Revlon Health Care Group Tuckahoe, NY, USA CONGRESS ORGANIZING COMMITTEE Sigurd Normann, Department of Pathology, University of Florida, Gainesville, Florida 32610/USA Ernst Sorkin, Schweizerisches Forschungsinstitut, Medizinische Abteilung, 7270 Davos-Platz/Switzerland David Wilkins, Centre de Recherche Merrell, 16, rue d~Ankara, 67084 Strasbourg-Cedex/France