Table Of ContentPlatelet-Activating
Factor and Related
Lipid Mediators
Platelet-Activating
Factor and Related
Lipid Mediators
Edited by
Fred Snyder
Oak Ridge Associated Universities
Oak Ridge, Tennessee
Plenum Press • New York and London
Library of Congress Cataloging in Publication Data
Platelet-activating factor and related lipid mediators.
Includes bibliographies and index.
1. Platelet activating factor. I. Snyder, Fred. [DNLM: 1. Platelet Activating Factor
metabolism. QU 93 P716]
QP752.P62P57 1987 612/.117 87-14198
ISBN-13: 978-1-4684-5286-0 e-ISBN-13: 978-1-4684-5284-6
001: 10.1007/978-1-4684-5284-6
© 1987 Plenum Press, New York
Softcover reprint ofthe hardcover 1 st edition 1987
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
ForJoy
Contributors
Wolfgang E. Berdel, M.D. • Division of Hematology and Oncology, Depart
ment of Medicine 1. Technical University, 8000 Munich 80, Federal Republic
of Germany.
Merle L. Blank, B.S. • Medical and Health Sciences Division, Oak Ridge
Associated Universities, Oak Ridge, Tennessee 3783l.
John E. Bleasdale, Ph.D. • University of Texas Health Science Center, Dallas,
Texas 75235.
Pierre Braquet, Ph.D., D.Se. • General Manager, Director of Research, Henri
Beaufour Institute, 92350 Le Plessis Robinson, France.
Jan R. Brentjens, M.D. • Department of Pathology, School of Medicine, State
University of New York, Buffalo, New York 14214.
Giovanni Camussi, M.D. • Department of Pathology, School of Medicine,
State University of New York, Buffalo, New York 14214.
Keith L. Clay, Ph.D. • Department of Pharmacology, University of Colorado
Health Sciences Center, Denver, Colorado 80262.
Thomas W. Doebber, Ph.D. • Merck, Sharp & Dohme Research Laboratories,
Rahway, New Jersey 07065.
Giora Feuerstein, M.D. • Neurobiology Research Division, Department of
Neurology, Uniformed Services University of the Health Sciences, Bethesda,
Maryland 20814-4799.
J. J. God/roid, D.Sc. • University of Paris 7, Laboratory of Molecular Phar
macochemistry, 75015 Paris, France.
Robert E. Goldstein, M.D. • Division of Cardiology, Department of Medicine,
Uniformed Services University of the Health Sciences, Bethesda, Maryland
20814-4799.
Julian Gomez-Cambronero, Ph.D. • Laboratory of Experimental Nephrology,
Institute of Investigational Medicine, 28040-Madrid, Spain.
J.
Donald Hanahan, Ph.D. • Department of Biochemistry, University of
Texas Health Science Center, San Antonio, Texas 78284-7760.
Peter M. Henson, Ph.D. • Department of Pediatrics, National Jewish Center
for Immunology and Respiratory Medicine, Denver, Colorado 80206.
vii
viii Contributors
Dennis R. H of/man, Ph.D. • Department of Biochemistry, University of Texas
Health Science Center, Dallas, Texas 75235.
San-Bao Hwang, Ph.D. • Merck, Sharp & Dohme Research Laboratories,
Rahway, New Jersey 07065.
Pedro Iiiarrea, Ph.D. • Laboratory of Experimental Nephrology, Institute of
Investigational Medicine, 28040-Madrid, Spain.
John M. Johnston, Ph.D. • Department of Biochemistry, University of Texas
Health Science Center, Dallas, Texas 75235.
Raj Kumar, Ph.D. • Department of Biochemistry, University of Texas Health
Science Center, San Antonio, Texas 78284-7760.
Ten-Ching Lee, Ph.D. • Medical and Health Sciences Division, Oak Ridge
Associated Universities, Oak Ridge, Tennessee 37831.
Jean Michel Mencia-Huerta, Ph.D. • INSERM U200, University of South
Paris, 92140 Clamart, France.
Thomas M. McIntyre, Ph.D. • Department of Internal Medicine, The Nora
Eccles Harrison Cardiovascular Research and Training Institute, University of
Utah School of Medicine, Salt Lake City, Utah 84112.
P. G. Munder, M.D. • Max Planck Institute for Immunobiology, 78 Freiburg,
I.BR., Federal Republic of Germany.
Robert C. Murphy, Ph.D. • Department of Pharmacology, University of Colo
rado Health Sciences Center, Denver, Colorado 80262.
Ewa Ninio, Ph.D. • INSERM U200, University of South Paris, 92140 Clam
art, France.
Joseph T. O'Flaherty, M.D. • Department of Medicine, Wake Forest Univer
sity Medical Center, Winston-Salem, North Carolina 27103.
Stephen M. Prescott, M.D. • Department of Internal Medicine, The Nora Ec
cles Harrison Cardiovascular Research and Training Institute, University of
Utah School of Medicine, Salt Lake City, Utah 84112.
James C. Robbins, Ph.D. • Membrane and Arthritis Research, Merck, Sharp &
Dohme Research Laboratories, Rahway, New Jersey 07065.
Mitchell Robinson, Ph.D. • Medical and Health Sciences Division, Oak Ridge
Associated Universities, Oak Ridge, Tennessee 37830.
Mariano Sanchez-Crespo, M.D., Ph.D. • Laboratory of Experimental Nephrol
ogy, Institute of Investigative Medicine, 28040-Madrid, Spain.
T. Y. Shen, Ph.D., D.Sc. • Department of Chemistry, University of Virginia,
Charlottesville, Virginia 22901.
Fred Snyder, Ph.D. • Medical and Health Sciences Division, Oak Ridge Asso
ciated Universities, Oak Ridge, Tennessee 37831.
Takayuki Sugiura, Ph.D. • Faculty of Pharmaceutical Sciences, Teikyo Uni
versity, Sagamiko, Kanagawa, 199-01 Japan.
Frank H. Valone, M.D. • Hematology/Oncology Section (lIIK), Veterans
Administration Medical Center, San Francisco, California 94121.
B. B. Vargaftig, Ph.D. • Pasteur Institute, INSERM U285, 75015 Paris,
France.
Contributors ix
Keizo Waku, Ph.D. • Faculty of Pharmaceutical Sciences, Teikyo University,
Sagamiko, Kanagawa, 199-01 Japan.
Robert L. Wykle, Ph.D. • Department of Biochemistry, Bowman Gray School
of Medicine of Wake Forest University, Winston-Salem, North Carolina
27103.
Guy A. Zimmerman, M.D. • Department of Internal Medicine, The Nora Ec
cles Harrison Cardiovascular Research and Training Institute, University of
Utah School of Medicine, Salt Lake City, Utah 84112.
Preface
Platelet-activating factor (PAF) is the commonly used name for a group of potent
biologically active, ether-linked phospholipids, the alkylacetylglycerophospho
cholines. Following the identification of the chemical structure of P AF in 1979,
much progress has been made in our understanding of these phospholipid medi
ators. This is particularly true from the points of view of their molecular structural
requirements for expression of biological activity, their biosynthesis and cata
bolism, their diverse range of biological activities, evidence for their specific recep
tors at the cell surface, the development of specific antagonists for use in receptor
studies and for testing as potential anti-PAF drugs, and implications about their
involvement in health and disease. Chapters in this book cover the current status of
these general areas of PAF research. Although an enormous amount of information
has been published about this interesting new type of phospholipid mediators,
questions about their mechanism of action, regulatory controls, and the precise role
and relative importance of P AF in specific diseases and physiological functions
remain to be answered.
Since the 1979 discovery, the PAF field has brought together scientists from a
variety of different biomedical disciplines. The diversity of scientists now in PAF
research is very apparent from the number of P AF publications appearing in a wide
array of scientific journals, ranging from molecular biology to clinical medicine.
Publications related to PAF continue to increase at an amazingly rapid rate, with the
pace reminiscent of the period following the discovery of prostaglandins. Two
international conferences devoted exclusively to PAF have been successfully staged
since 1983. Many other smaller conferences and symposia held annually have also
included specific sessions on PAF, which further emphasizes the broad interest and
curiosity that has surrounded these novel bioactive phospholipids.
The difficulties in comprehending and cementing together all of the isolated
tidbits of information in the PAF jigsaw puzzle are the main reason why this first
book on the subject has been published. I felt that PAF research had advanced to a
point where a single volume of chapters from key laboratories in the field was
necessary to summarize the many isolated publications that cover a broad scope of
PAF research topics. It also seemed that such a volume would provide the best
xi
xii Preface
current assessment of the field by those scientists who have made major contribu
tions to our current knowledge about PAF and structurally related lipids. Further
more, a compiehensive book on the acetylated alkyl ether phospholipids especially
seemed appropriate at this time since no single review article can adequately cover
the extensive literature or give a critical assessment of all research areas in the field.
This volume should also provide a historical record of significant develop
ments in PAF research that have occurred up to now. Thus, even though the current
pace of PAF research moves like a rocket into the unknown, the chapters do
represent a thorough review of the early portion of the PAF era that should be useful
both to experienced P AF researchers and to newcomers to this exciting area of lipid
research. Moreover, I expect this book will be an excellent source of information
for teachers and students who are not directly involved in PAF research but who
partake in advanced courses dealing with biochemistry of lipid mediators in mam
malian cells.
Fred Snyder
Oak Ridge, Tennessee
Description:Platelet-activating factor (PAF) is the commonly used name for a group of potent biologically active, ether-linked phospholipids, the alkylacetylglycerophospho cholines. Following the identification of the chemical structure of P AF in 1979, much progress has been made in our understanding of thes
