THE NEUTROPHILS: NEW OUTLOOK FOR OLD CELLS

This page is intentionally left blank

THE NEUTROPHILS: NEW OUTLOOK FOR OLD CELLS Editor Dmitry I Gabrilovich Vanderbilt University School of Medicine Imperial College Press

Published by Imperial College Press 203 Electrical Engineering Building Imperial College London SW7 2BT Distributed by The Neutrophils: New Outlook for Old Cells Downloaded from www.worldscientific.com World Scientific Publishing Co. Pte. Ltd. P O Box 128, Fairer Road, Singapore 912805 USA office: Suite IB, 1060 Main Street, River Edge, NJ 07661 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. THE NEUTROPfflLS: NEW OUTLOOK FOR OLD CELLS Copyright 1999 by Imperial College Press All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the Publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. ISBN 1-86094-082-X This book is printed on acid-free paper. Printed in Singapore by Uto-Print

To my dad and first friend Isaak V

PREFACE This book is about one cell, the polymorphonuclear neutrophil. But at the same time this book is also about all human cells and the organism itself, since the neutrophil as no other cell is involved in maintaining homeostasis of an organism. It is not simply because of their abundance (more than 2 x 10 10 cells in circulation), but mainly because these cells are able to perform numerous functions. They produce free radicals, phagocytize microorganisms, secrete a number of cytokines, kill tumor cells, neutralize viruses, etc. Over the past 100 years, this cell has witnessed times of intense interest and great expectations and periods when that interest waned. The major breakthrough in neutrophil research happened between the 1880s and 1920s (discovery of "polynuclear cells" by Paul Ehrlich and pioneering groundwork by Ilya Metchnikoff). The neutrophil was at the epicenter of intensive discussion about the nature of immunity and was considered by many as a most crucial player in immune response. Although studies of neutrophils continued in following years in brilliant works by Ado, Karnovsky, Becker and many others, this cell slowly but steadily was upstaged by lymphocytes and macrophages. With new information emerging about the roles of lymphocytes and macrophages in immune response, the appearance of new techniques to clone antigen-specific lymphocytes, identification of different lymphocyte subsets etc., the neutrophil was pushed out of the spotlight and on to the periphery of discussion. It was considered mostly as a vehicle for bacterial phagocytosis. Neutrophil had fallen out of fashion. Sic transit gloria mundl However, times change again. New major breakthroughs in neutrophil research started about 20 years ago and continue today. It took the appearance Vll

Vlll The Neutrophils: New Outlook for Old Cells The Neutrophils: New Outlook for Old Cells Downloaded from www.worldscientific.com of new methods of molecular biology and biochemistry to revive interest in this cell. It turns out that the neutrophil has a fascinating biochemistry, able to secrete many factors and affect many physiological and pathological processes. This cell has become a very interesting model for investigation of general mechanisms of cell activation and metabolism, attracting the attention of many investigators. The number of publications in the scientific literature skyrocketed from 686 in 1966-1968 to 6837 in 1993-1995. For the same period of time the number of publications about lymphocytes increased 5 times and monocytes/ macrophages 8 times (Source: Medline search based on keywords). In preparing this monograph, authors tried to pursue two major aims. First, to provide readers with a detailed overview of the recent developments in neutrophil research, as well as to present some topics that have never been discussed in monographs before. Second, to draw the attention of a broad spectrum of researchers from other fields and clinical scientists to this incredible cell, to demonstrate how much neutrophil can give in return for exploration by inquisitive minds. This monograph consists of two blocks. The first, larger block, describes basic neutrophil biology and the second, smaller one, shows how our knowledge of neutrophil biology can be applied in practical medicine. In the first chapter of this monograph, Dr. English discusses in detail the molecular basis of neutrophil activation, demonstrating why neutrophils may serve as a unique model for investigation of basic mechanisms of cell activation. Dr. Heinecke describes the current status of our knowledge of probably the most important functional feature of these cells respiratory burst. Readers will find information about relatively new players in this field, as well as well known factors such as NADPH and myeloperoxidase. A very important characteristic of these cells is their ability to migrate to the site of infection or tissue injury. In the third chapter Dr. Zweier talks about mechanisms of neutrophil migration and the role of different receptors responsible for accumulation of these cells in tissues. Dr. Ferrante discusses the effect of fatty acids on neutrophil function, a new area of investigation that may potentially have a significant impact not only on our understanding of neutrophil biology, but also on clinical medicine. In the next chapter, Dr. Casatella presents an exhaustive overview of soluble factors released by neutrophils in response to different stimuli and their impact on functioning of other cells. Drs. Fanning,

Preface IX The Neutrophils: New Outlook for Old Cells Downloaded from www.worldscientific.com Redmond and Bouchier-Hayes describe the mechanisms and significance of apoptosis, an important mechanism of neutrophil death. The first block concludes with an overview by Dr. Rot of chemokine receptors, an interesting element in neutrophil function. Accurate use of laboratory techniques and correct interpretation of the results are critically important in clinical practice. In the opening chapter of the second block Dr. Virella discusses available methods for evaluation of neutrophil function. In the next chapter Dr. Roberts gives an overview of the role of neutrophils in the anti-viral response, discussing in detail neutrophil function in HIV and influenza virus infections. The last two chapters address how to improve defective neutrophil function in certain diseases. Drs. Dale and Nelson discuss the use of colony-stimulating factors in the treatment of neutropenia and infectious diseases. Benefits and possible pitfalls of neutrophil transfusion therapy are reviewed by Dr. Strauss. This book is the result of the collective effort of a group of scientists. I am extremely grateful to the individual contributors to this book, who kindly found time in the midst of their active research and clinical duties to share with us their knowledge and thoughts. Dmitry Gabrilovich Vanderbilt University, Nashville, TN, USA

LIST OF CONTRIBUTORS Dr. D. Bouchier-Hayes, Department of Surgery, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland Dr. Marco A. Cassatella, Institute of General Pathology, Medical School, University of Verona, Verona, Italy Dr. David C. Dale, University of Washington Seattle, WA, USA Dr. Denis English, Bone Marrow Research Laboratory Experimental Cell Research Program Methodist Research Institute Indianapolis, IN, USA Dr. N.F. Fanning, Department of Surgery, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland Dr. Antonio Ferrante, Department of Immunopathology, The Women's and Children's Hospital and the University of Adelaide, 72, King William Road, North Adelaide, S A 5006, Australia Dr. Dmitry Gabrilovich, Vanderbilt University, Nashville, TN, 37232-6838, USA Dr. Jay W. Heinecke, Department of Medicine and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA XI

Xll The Neutrophils: New Outlook for Old Cells Dr. Charles S.T. Hii, Department, of Immunopathology, The Women's and Children's Hospital and the University of Adelaide, 72, King William Road, North Adelaide, S A 5006, Australia The Neutrophils: New Outlook for Old Cells Downloaded from www.worldscientific.com Dr. Zhi H. Huang, Department of Immunopathology, The Women's and Children's Hospital and the University of Adelaide, 72, King William Road, North Adelaide, S A 5006, Australia Dr. Steve Nelson, Louisiana State University Medical Center, New Orleans, LA, USA Dr. Deborah A, Rathjen, Department of Immunopathology, The Women's and Children's Hospital and the University of Adelaide, 72, King William Road, North Adelaide, S A 5006, Australia Dr. H. Paul Redmond, Department of Surgery, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland Dr. Robert L. Roberts, Division of Immunology/Allergy, UCLA School of Medicine, Los Angeles, CA, USA Dr. Antal Rot, Sandoz Research Institute, Vienna, Austria Dr. Ronald G. Strauss, University of Iowa College of Medicine, Iowa City, IA, USA Dr. Gabriel Virella, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, S.C., USA Dr. Jay L. Zweier, Molecular and Cellular Biophysics Laboratories, Department of Medicine, Division of Cardiology and the Electron Paramagnetic Resonance Center, The Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Preface List of Contributors CONTENTS Chapter 1 Molecular Basis of Neutrophil Activation 1 D. English Chapter 2 The Respiratory Burst of Neutrophils: Oxidative 31 Pathways for the Initiation of Tissue Damage at Sites of Inflammation J. W. Heinecke Chapter 3 Mechanism of Leukocyte Accumulation in 59 Postischemic Tissues: Role of Oxygen Free Radicals J. L. Zweier Chapter 4 Regulation of Neutrophil Functions by Fatty Acids 79 A. Fen-ante, C. S. T. Hii, Z. H. Huang, D. A. Rathjen Chapter 5 Production of Cytokines by Polymorphonuclear 151 Neutrophils M. A. Cassatella vii xi Chapter 6 Neutrophils and Apoptosis 231 N. F. Fanning, H. P. Redmond arid D. Bouchier-Hayes Xlll

xiv The Neutrophils: New Outlook for Old Cells Chapter 7 Neutrophil Migration and Methods for its 243 in vitro Study A. Rot Chapter 8 Diagnostic Evaluation of Neutrophil Function 275 G. Virella The Neutrophils: New Outlook for Old Cells Downloaded from www.worldscientific.com Chapter 9 Neutrophils in Viral Infections 299 R. L. Roberts Chapter 10 Use of Colony-Stimulating Factors for 319 Treatment of Neutropenia and Infectious Diseases D. C. Dale and S. Nelson Chapter 11 Neutrophil Transfusion Therapy 345 R. G. Strauss