Biochemistry of Inflammation

Transcription

1 Biochemistry of Inflammation

2 IMMUNOLOGY AND MEDICINE SERIES Immunology of Endocrine Diseases Editor: A. M. McGregor Clinical Transplantation: Current Practice and Future Prospects Editor: G. R. D. Catto Complement in Health and Disease Editor: K. Whaley Immunological Aspects of Oral Diseases Editor: L. Ivanyi Immunoglobulins in Health and Disease Editor: M. A. H. French Immunology of Malignant Diseases Editors: V. S. Byers and R. W. Baldwin Lymphoproliferative Diseases Editors: D. B. Jones and D. H. Wright Phagocytes and Disease Editors: M. S. Klempner, B. Styrt and J. Ho Immunology of Sexually Transmitted Diseases Editor: D. 1. M. Wright Mast Cells, Mediators and Disease Editor: S. T. Holgate Immunodeficiency and Disease Editor: A. D. B. Webster Immunology of Pregnancy and its Disorders Editor: C. M. M. Stern Immunotherapy of Disease Editor: T. 1. Hamblin Immunology of Prophylactic Immunization Editor: A. J. Zuckerman Immunology of Eye Disease Editor: S. Lightman Lymphoproliferative Diseases Editors: D. B. Jones and D. H. Wright Immunology of Renal Diseases Editor: C. D. Pusey Immunology of HIV Infection Editor: A. G. Bird Biochemistry of Inflammation Editors: 1. T. Whicher and S. W. Evans Immunology of Gastrointestinal Diseases Editor: T. T. MacDonald Immunology of ENT Disorders Editor: G. Scadding Immunology of Infection Editors: 1. G. P. Sissons, 1. Cohen and L. K. Borysiewicz

3 IMMUNOLOGV. SERIES. SERIES. SERIES. SERIES ANO SERIES SERIES. SERIES. SERIES MEDICI NE Volume 18 Biochemistry of InflammatÎon Edited by J. T. Whicher and s. w. Evans Department of Chemical Pathology and Immunology Old Medical School, Leeds, Series Editor: K. Whaley SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

4 Britisb Library Cataloguing in Publication Data Biochemistry of inflammation. - (Immunology and medicine; 18) 1. Whicher, J. T. II. Evans, S. W. III. Series ISBN Library of Coogress Cataloging-in-Publication Data Biochemistry of infiammation/edited by J. T. Whicher and S. W. Evans. p. cm. - (Immunology and medicine series; v. 18) Includes bibliographical references and index. ISBN ISBN (ebook) DOI / Infiammation - Pathophysiology. 2. Infiammation - Mediators. 1. Whicher, J. T. II. Evans, S. W. III. Series. [DNLM: 1. Acute Phase Proteins-physiology. 2. Complement-physiology. 3. Complement Activation-physiology. 4. Cytokines-physiology. 5.lnfiammation-immunology. 6.lnfiammation-physiopathology. Wl lm53bi v. 18] RB131.B '.0473-dc20 DNLMjDLC for Library of Congress CIP Copyright 1992 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 1992 Softcover reprint ofţhe hardcover Ist edition 1992 AlI rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers, Springer Science+Business Media, B.V. Typeset by Technical Keying Services, Manchester.

5 Contents Series Editor's Foreword Preface List of Contributors Vll ix Xl 1 An overview of the inflammatory response 1 S. W. Evans and J. T. Whicher 2 The complement system and inflammation 17 A. R. McPhaden and K. Whaley 3 The kinin system: current concepts and perspectives 37 D. Regoli, N.-E. Rhaleb, G. Drapeau and S. Dion 4 Role of cellular proteinases and their protein inhibitors in inflammation 57 J. F. Woessner, Jr. 5 Eicosanoids (prostaglandins and leukotrienes) 91 E. R. Pettifer, G. A. Higgs and J. A. Salmon 6 The role of toxic oxygen species in inflammation with special reference to DNA damage 109 P. G. Winyard, D. Perrett, G. Harris and D. R. Blake 7 Glucocorticoids and lipocortin 131 S. H. Peers and R. J. Flower 8 Platelet activating factor and cytokine feedback regulation of endothelial integrity: implications for the treatment of inflammatory disease 147 D. Hosford, M. Paubert-Braquet and P. Braquet 9 A role for neuropeptides in inflammation 177 C. W. Denko v

6 CONTENTS 10 Interleukin 1 as an inflammatory mediator 183 J. A. Symons, J. A. Eastgate and G. W Duff 11 Tumour necrosis factor (TNF) and inflammation 211 P. J. McLaughlin 12 Interleukin 6: a consequence of inflammation 225 S. W Evans 13 The acute phase response 243 J. T. Whicher and C. I. Westacott 14 The role of leukocyte chemotaxis in inflammation 271 A. Rot Index 305 vi

7 Series Editor's Foreword The interface between clinical immunology and other branches of medical practice is frequently blurred and the general physician is often faced with clinical problems with an immunological basis and is expected to diagnose and manage such patients. The rapid expansion of basic and clinical immunology over the past two decades has resulted in the appearance of increasing numbers of immunology journals and it is impossible for a non-specialist to keep apace with this information overload. The Immunology and Medicine series is designed to present individual topics of immunology in a condensed package of information which can be readily assimilated by the busy clinician or pathologist. K. Whaley, Glasgow August 1991 vii

8 Preface In the last 10 years our understanding of inflammation has increased dramatically. As with most other areas of medical science, this has in large part been due to the impact of molecular biology and to our ability to identify and clone the genes for many important intercellular mediators. It is evident that inflammation is a complex and concerted response of the organism to foreign bodies or tissue damage. Many cell types from the classical inflammatory cells to tissue cells are involved and they communicate via a multitude of different systems. The study of inflammation can be approached from many directions and it is the purpose of this book to bring together ideas from a number of different bichemical disciplines which are frequently not integrated. The first chapter describes visually the main issues addressed within the book and will, we hope, prove valuable as an overview of this complex subject. The remaining chapters have been organized into three themes: the affector molecules, the regulatory components and the processes of inflammation itself. The affector molecules are epitomized by the complement system, now regarded as playing an essential role in inflammation, and from a biochemical standpoint one of the best understood mediator systems. The kinins, long known to induce vascular permeability in inflammation, have now become recognized as key effector molecules with the realization that they may be produced by kallikreins both in the plasma and from tissue cells, notably the polymorphonuclear leukocyte. This brings them into the family of mediators directly produced by the activity of inflammatory cells. A number of the mediator systems of inflammation such as complement and coagulation are comprised of cascades of proteolytic enzymes. They are thus highly susceptible to activation by proteases released from cells. These are present in the lysosomes and also in a complex array of granules in some inflammatory cell types. Much of the damage produced by inflammation and the remodelling which follows is dependent upon the release of proteolytic enzymes from both inflammatory cells and tissue cells. In addition, there is increasing evidence that proteases contribute to various intracellular control mechanisms. Not surprisingly in such a complex situation a bewildering array of inhibitors exists. The importance of these complex systems is only now beginning to be appreciated. The importance of locally produced prostaglandins in inflammaix

9 PREFACE tion has been well recognized for many years and indeed has been the basis for much of the pharmacological intervention in the processes of inflammation. Recently, it has become clear that besides these classic mediators a number of other extremely important products of arachidonic acid metabolism, especially platelet activity factor, playa part in inflammation. Production of reactive oxygen species is the key process in the development of inflammatory damage. These molecules are necessary for bacteriological activity of phagocytic cells; however it is now recognized that oxygen-derived products, particularly in the joint, may be key mediators in the chronic damage which follows inflammation. While many of the mediators and affector molecules of inflammation have been known about and investigated for many years, the regulatory molecules are only now being unravelled. It is clear that glucocorticoids, previously thought of as simple immunosupressive hormones, are intricately involved in the normal control mechanisms regulating inflammation and the response to trauma. Not only is the secretion of these hormones controlled by inflammatory products, such as interleukin 1 and interleukin 6, but they have complex functions in regulating the activity of immune and inflammatory cells. Platelet activating factor is a powerful endogenous mediator which not only behaves locally as an inflammatory mediator in a manner analogous to kinins and prostaglandins but also is increasingly being shown to act systematically with functions analogous to the cytokines. The cytokines primarily involved in inflammation, interleukin 1, tumour necrosis factor and interleukin 6, have both local effects in the control of inflammatory cells and post-inflammatory remodelling, and important systemic effects on the vascular, nervous and endocrine systems adjusting the 'milieu interieur' of the organism and optimizing the inflammatory process. The last two chapters describe the process of inflammation. Whilst inflammation may be thought of as an essentially local process it is clear that systemic effects (often called the acute phase response) occur. These effects, including changes in body temperature, vascular permeability, circulating hormones, acute phase protein synthesis and leukocytosis, are considered in the penultimate chapter. All these processes alter local inflammation in a complex way but have probably evolved to optimize its function or more provocatively to minimize inflammatory damage. At the local level inflammation is based on complex patterns of cell recruitment and activation. This important basis of the local inflammatory response is described in the final chapter. x

10 List of Contributors D.R.BLAKE Bone and Joint Research Unit London Hospital Medical College Ashfield Street London El lad P. BRAQUET Institut Henri Beaufour 17, avenue Descartes Le Plessis Robinson France C. W. DENKO Department of Medicine/Rheumatology Case Western Reserve University University Hospitals of Cleveland Cleveland, OH USA S. DION Department of Pharmacology Medical School University of Sherbrooke Sherbrooke J1H 5N4 Canada G.DRAPEAU Department of Pharmacology Medical School University of Sherbrooke Sherbrooke J1H 5N4 Canada G. W. DUFF Section of Molecular Medicine Department of Medicine and Pharmacology University of Sheffield Royal Hallamshire Hospital Sheffield S10 2JF J. A. EASTGATE Section of Molecular Medicine Department of Medicine and Pharmacology University of Sheffield Royal Hallamshire Hospital Sheffield S10 2JF S. W. EVANS Department of Chemical Pathology and Immunology Old Medical School University of Leeds Leeds LS2 9JT G. HARRIS Department of Immunology London Hospital Medical College Turner Street London El 2AD G. A. HIGGS Celltech Ltd. 216 Bath Road Slough, Berks. SL 1 4EN D.HOSFORD Institut Henri Beaufour 17, avenue Descartes Le Plessis Robinson France P. J. MCLAUGHLIN Department of Immunology University of Liverpool PO Box 147 Liverpool L69 3BX xi

11 LIST OF CONTRIBUTORS A. R. McPHADEN Department of Pathology Western Infirmary Glasgow G116NT M. PAUBERT-BRAQUET Institut Henri Beaufour 17. avenue Descartes Le Plessis Robinson France S.H.PEERS Department of Biochemical Pharmacology St Bartholomew's Hospital Medical College Charterhouse Square London EC1M 6QB D.PERRETT Department of Medicine St Bartholomew's Hospital Medical College West Smithfield London EC1A 7BE E. R. PETTIPHER Department of Immunology and Infectious Diseases Pfizer Central Research Groton Connecticut USA D. REGOLI Department of Pharmacology Medical School University of Sherbrooke Sherbrooke J1H 5N4 Canada N.-E. RHALEB Department of Pharmacology Medical School University of Sherbrooke Sherbrooke J1H 5N4 Canada J. A. SALMON Department of Pharmacology Well come Research Laboratories Langley Court Beckenham Kent BR3 3BS J. A. SYMONS Section of Molecular Medicine Department of Medicine and Pharmacology University of Sheffield Royal Hallamshire Hospital Sheffield S10 2JF C. I. WESTACOTT Department of Chemical Pathology and Immunology Old Medical School University of Leeds Leeds LS2 9JT K. WHALEY Department of Pathology Western Infirmary. Glasgow G11 6NT J. T. WHICHER Department of Chemical Pathology and Immunology Old Medical School University of Leeds Leeds LS2 9JT P. G. WINYARD Bone and Joint Research Unit London Hospital Medical College Ashfield Street London E1 1AD J. F. WOESSNER, JR Department of Biochemical and Molecular Biology University of Miami School of Medicine Miami FL USA A.ROT Sandoz Forschungsinstitut Vienna Austria xii