Table Of ContentThe Neutrophil:
Cellular Biochemistry
and Physiology
Editor
Maurice B. Hallett, Ph.D.
Senior Lecturer in Immunology
University Department of Surgery
University of Wales College of Medicine
Cardiff, U.K.
Boca Raton London New York
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Library of Congress Cataloging-in-Publication Data
The Neutrophil: cellular biochemistry and physiology / editor,
Maurice B. Hallett.
p. cm.
Bibliography: p.
Includes index.
ISBN 0-8493-4808-0
1. Neutrophils. I. Hallett, Maurice B. (Maurice Bartlett), 1952-
QR185.8.N47N46 1989
612’ . 112—dc19 88-2603
A Library of Congress record exists under LC control number: 88002603
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Dedicated
to Jill, Jenny, and Tim.
PREFACE
The importance of neutrophils in combating infectious disease is dramatically demonstrated
in chronic granulomatous disease. In this condition, neutrophils and macrophages fail to
effectively kill infecting microbes. The consequences of this failure are catastrophic and
fatal. Without effective neutrophils, the balance between the microbes and the animal swings
greatly towards the microbe. Arguably, the evolution of man, therefore, has depended upon
the efforts of these cells to keep the microbiological environment at bay. It is also being
recognized that, in some situations, the "weapons" normally used in the fight against
microbes can become directed against surrounding tissue. The resulting tissue damage may
underlie many of the inflammatory diseases. Understanding of the mechanisms by which
neutrophils perform their crucial antimicrobial role in health and the mechanisms that induce
their aberrant behavior in disease is therefore of great importance.
As a consequence, there are a great many reviews on specific areas of interest within the
cell. For example, some recent and important reviews have been given by Tauber,' Sklar
and colleagues,2 and Sha'afi and Molski.3 An excellent and comprehensive review of the
knowledge and state of understanding of the neutrophil (to 1977) has also been given in the
book by Klebanoff and Clark.4 However, since its publication, many great strides have been
made towards understanding the mechanisms that control neutrophil activity.
Over the past 5 years, there has been a massive increase in our understanding of the ways
in which stimuli evoke cellular responses. The expansion of knowledge is also reflected in
the number of publications on the subject of neutrophils, rising from approximately 500 in
1977 to over 1000 in 1986. The aim of this book is to condense much of this important
information concerning signal response coupling in neutrophils into a view of the cellular
The neutrophil with some of the important intracellular constituents discussed in this
volume shown. The reactions and relationships between them have been left deliberately
ambiguous. After completion of this volume, the reader may perhaps feel confident about
putting in a few definite arrows and even add a few speculative ones. (Space is also left
for the inclusion of further components as their importance and identities becomes
established.)
mechanisms that enables the cellular biochemistry and physiology to be understood within
a conceptual framework. In areas where no such framework is clearly defined, it is hoped
that the perspectives given will enable questions to be asked and answers sought. Despite
the necessary process of condensation of the welter of data, each chapter has attempted to
give a comprehensive review of its topic, over 1500 references being given in this volume.
After the first chapter, in which some historical perspective to the study of neutrophils is
given, together with an attempt to explore mechanisms for failure in pathological conditions
for neutrophils, the first part of the text describes some of the cellular and intracellular events
that result from the stimulation of neutrophils, i.e., chemotaxis, secretion, oxidase activation,
arachidonate production, and cytoskeletal rearrangement during both phagocytosis and chemo-
taxis. The second part of the book concentrates on the mechanisms that couple stimulation
to response, and includes discussion of intracellular Ca2+ and its relation to other intracellular
changes, including kinase activation, phospholipid metabolism, and membrane electro-
physiological changes.
REFERENCES
1. Tauber, I. A. Protein kinase C and the activation of the human neutrophil NADPH-oxidase, Blood, 69,
711, 1987.
2. Omaann, G. M., Allen, R. A., Bokoch, G. M., Painter, R. G., Traynor, A. E., and Sklar, L. A.,
Signal transduction and cytoskeletal activation of the neutrophil, Physiol. Rev., 67, 285, 1987.
3. Sha'afi, R. I. and Molski, T. F. P. Activation of the neutrophil, in Progress in Allergy, Vol. 39, Ishizaka,
K., Kallos, P., and Waksman, B. H., Eds., S. Karger, Basel, 1987.
4. Klebanoff, S. J. and Clark, R. A., The Neutrophil: Function and Clinical Disorders, North-Holland,
Amsterdam, 1978.
THE EDITOR
Maurice B. Hallett is Senior Lecturer in Immunology at the University of Wales College
of Medicine in Cardiff, U.K. He studied at University College London, receiving a B.Sc.
in Pharmacology in 1974 and his Ph.D. in 1978. During this time, Dr. Hallett developed a
strong interest in the intracellular mechanisms that control cell activation, particularly with
the aim of understanding the manner in which alterations of cell signaling processes lead to
allergic and inflammatory disease. This interest was strengthened at the Welsh National
School of Medicine, where his research focused on the intracellular biochemistry and phys-
iology of the neutrophil. He was appointed Lecturer at the University of Wales College of
Medicine in 1984 and Senior Lecturer in 1987.
Dr. Hallett belongs to several scientific societies, including the Biochemical Society, the
British Society for Cell Biology, the British Society for Immunology, and the Institute of
Biology. His current research involves measurement of intracellular processes within living
neutrophils taken from both normal and pathological tissues.
CONTRIBUTORS
Futwan A. Al-Mohanna Hans Gruler, Ph.D.
Research Officer Professor of Physics
Department of Surgery Department of Biophysics
University of Wales University of Ulm
College of Medicine Ulm, West Germany
Cardiff, Wales
Maurice Bartlett Hallett, Ph.D.
Pierre Borgeat, Ph.D.
Senior Lecturer in Immunology
Professor
Department of Surgery
Unite de Recherche, Inflammation
University of Wales
et Immunologie-Rhumatologie
College of Medicine
Centre Hospitalier de l'Universite Laval
Cardiff, U.K.
Quebec, Canada
Owen T. G. Jones, Ph.D.
Shamshad Cockcroft, Ph.D.
Professor
Lecturer
Department of Biochemistry
Department of Experimental Pathology
School of Medicine
School of Medicine
University of Bristol
University College of London
Bristol, England
London, England
Eryl Cooke, Ph.D. Daniel P. Lew, M.D.
Research Fellow Professor
Department of Surgery Department of Infectious Diseases
University of Wales Hopital Cantonal
College of Medicine Geneva, Switzerland
Cardiff, Wales
Leslie C. McKinney, Ph.D.
Andrew Richard Cross, Ph.D.
Research Physiologist
Postdoctoral Research Associate
Department of Physiology
Department of Biochemistry
Armed Forces Radiobiology Research
School of Medicine
Institute
University of Bristol
National Naval Medical Center
Bristol, England
Bethesda, Maryland
Francesco Di Virgilio, M.D.
Paul H. Naccache, Ph.D.
Associate Professor
Associate Professor
Department of General Pathology
Unite de Recherche, Inflammation et
University of Padova
Immunologie-Rhumatologie
Padova, Italy
Centre Hospitalier de l'Universite Laval
Quebec, Canada
Elaine K. Gallin, Ph.D.
Head of Cellular Physiology Division
Department of Physiology Tullio Pozzan, M.D..
Armed Forces Radiobiology Research Professor
Institute Department of General Pathology
National Naval Medical Center University of Ferrara
Bethesda, Maryland Ferrara, Italy
Janet E. Rickard, Ph.D. P. Sheterline, Ph.D.
NATO Research Fellow Senior Lecturer
Department of Cell Biology Department of Medical Cell Biology
E. M. B. L. University of Liverpool
Heidelberg, West Germany Liverpool, England
Ramadan I. Sha'afi, Ph.D. James E. Smolen, Ph.D.
Professor Associate Professor
Department of Physiology Departments of Pediatrics and Pathology
University of Connecticut Health Center University of Michigan Hospitals
Farmington, Connecticut Ann Arbor, Michigan
Susan Treves, M.Sc.
Ph.D. candidate
Department of General Pathology
University of Padova
Padova, Italy
TABLE OF CONTENTS
Chapter 1
The Significance of Stimulus-Response Coupling in the Neutrophil for Physiology
and Pathology 1
Maurice B. Hallett
Chapter 2
Characteristics and Mechanisms of Secretion by Neutrophils 23
James E. Smolen
Chapter 3
Biophysics of Leukocytes: Neutrophil Chemotaxis, Characteristics and Mechanisms 63
Hans Gruler
Chapter 4
The Molecular Mechanism of Oxygen Reduction by the Neutrophil Oxidase 97
Andrew Richard Cross and Owen T. G. Jones
Chapter 5
Mobilization, Metabolism, and Biological Effects of Eicosanoids in
Polymorphonuclear Leukocytes 113
Paul H. Naccache, Ramadan I. Sha'afi, and Pierre Borgeat
Chapter 6
The Cortical Actin Filament Network of Neutrophil Leukocytes during Phagocytosis
and Chemotaxis 141
Peter Sheterline and Janet E. Rickard
Chapter 7
The Role of Inositol Phospholipid Metabolism and Diacylglycerol Production in
Neutrophil Signal Transduction 167
Shamshad Cockcroft
Chapter 8
Role of Calcium in Neutrophil Activation 199
Francesco Di Virgilio, Susan Treves, Daniel Lew, and Tullio Pozzan
Chapter 9
Ca2 +-Dependent and Independent Mechanisms in Neutrophil Activation; Roles of
Kinase C, Diacylglycerol, and Unidentified Intracellular Messengers 219
E. Cooke, F. A. AI-Mohanna, and M. B. Hallett
Chapter 10
Ion Transport in Phagocytes 243
Elaine Gall in and Leslie C. McKinney
Index 261
