Table Of ContentCell Signaling in Vascular Inflammation
I n f e c t i o u s . D i s e a s e
Cell Signaling
in Vascular
Inflammation
Edited by
Jahar Bhattacharya, ,
MBBS DPhil
Professor of Physiology and Cellular Biophysics,
Clinical Physiological Medicine,
and Medicine, Columbia University, New York, NY
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Library of Congress Cataloging in Publication Data
Cell signaling in vascular inflammation / edited by Jahar Bhattacharya.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-525-7 (alk. paper)
1. Vasculitis 2. Cellular signal transduction. 3. Inflammation--Mediators.
[DNLM: 1. Vasculitis--pathology. 2. Intercellular Signaling Peptides and
Proteins. 3. Paracrine Communication--physiology. WG 515 C393 2005] I. Bhattacharya, Jahar.
RC694.5.I53C45 2005
616.1'3--dc22
2004017975
Preface
Inflammatory disease of the lung vascular bed is a major cause of morbidity and
mortality in both adult and pediatric age groups. A particularly devastating consequence
of lung inflammation is lung injury, which alone accounts for 150,000 cases annually
in the United States, and carries a mortality rate of more than 30%. Yet, in the teaching
about lung inflammation and in its application to clinical practice, the importance of
vascular biology has been somewhat neglected.
Lung inflammation results from the defensive responses of pulmonary vascular cells
to pathogenic stimuli. The responses arise through signal transduction mechanisms,
which constitute sequences of intracellular events that lead up to specific cellular
responses. Secondary effects of such responses precipitate all of the phenotypic fea-
tures of lung inflammatory disease, including vascular hyperpermeability, white cell
accumulation, and vascular remodeling. An understanding of signal transduction path-
ways in lung vascular cells is therefore required not only to explain the processes of
lung inflammation, but also to develop new therapeutic strategies to combat inflamma-
tory lung diseases.
Although great strides have been made in the science of cell signaling, much of this
understanding is derived from nonlung cells. Consequently, the understanding is often
of tangential relevance to lung vascular biology. The lung’s unique position at the sys-
temic interface with the environment arms it with a sensitive immune defense capabil-
ity, a physiologically protective feature that also carries significant pathological risk.
This and other special features of the pulmonary circulation compel a studied and spe-
cific consideration of signal transduction processes in the context of lung vascular dis-
ease. It is my hope that Cell Signaling in Vascular Inflammation will foster better
awareness of these phenomena.
My intention in assembling these chapters has been to cut across disciplines to bring
together a broad-based presentation of inflammatory challenge, both in the initial
phases of the inflammatory response as also in the more prolonged phase of genomic
involvement. The chapters comprise a comprehensive survey of signaling processes.
Hence, the book will be useful to a broad spectrum of readers, including advanced
students of lung biology, investigators seeking new research directions, and clinicians
and scientists involved in lung inflammation and its management.
Finally, I would like to thank several people without whose help this volume would
not have been possible. I received advice and encouragement throughout from Drs.
Ken Weir, Jack Reeves, and Wiltz Wagner. Ms. Paige Walker of the American Heart
Association and my assistant, Ms. Rashmi Patel, provided outstanding support in get-
ting the material together and in ensuring its preparation for publication. My wife,
Sunita, supported me in many ways, not least through encouragement and patience.
Jahar Bhattacharya,MBBS,DPhil
v
Contents
Preface...................................................................................................................v
Contributors....................................................................................................... ix
1 Heme Oxygenase-1 and Carbon Monoxide in Vascular Regulation
Stefan W. Ryter and Augustine M. K. Choi ...................................................1
2 Tumor Necrosis Factor-(cid:70)/Receptor Signaling Through
the Akt Kinase
Osman Nidai Ozes, Hakan Akca, Jason A. Gustin, Lindsey D. Mayo,
Roxana Pincheira, Chandrashekhar K. Korgaonkar,
and David B. Donner .......................................................................................13
3 Protein Modifications by Nitric Oxide and Reactive Nitrogen Species
Harry Ischiropoulos .........................................................................................23
4 Redox Signaling in Hypoxic Pulmonary Vasoconstriction
E. Kenneth Weir, Zhigang Hong, Anthony Varghese,
Daniel P. Nelson, and Andrea Olschewski..............................................27
5 cGMP-Dependent Protein Kinase in Regulation
of the Perinatal Pulmonary Circulation
Usha Raj, Yuansheng Gao, Srinivas Dhanakoti, and Fred Sander.........35
6 Glutamate Receptor Activation in the Pathogenesis
of Acute Leg Injury
Sami I. Said ........................................................................................................47
7 Carboxyl Methylation of Small GTPases
and Endothelial Cell Function
Sharon Rounds, Elizabeth O. Harrington, and Qing Lu...........................51
8 Pressure-Induced Inflammatory Signaling
in Lung Endothelial Cells
Wolfgang M. Kuebler........................................................................................61
9 Regulation of Endothelial Barrier Function:
Contributions of the Transcellular and Paracellular Pathways
Dolly Mehta, Richard D. Minshall, and Asrar B. Malik ..........................73
10 Sphingolipid Signaling: Implications for Vascular Biology
Margaret M. Harnett........................................................................................91
11 Regulations of Cytokine Signaling
Bao Q. Vuong, Lisa McKeag, Julie A. Losman, Jianze Li,
Alex Banks, Scott Fay, Peter Chen, and Paul Rothman .....................103
vii
viii Contents
12 Cell Signaling by Vasoactive Agents
Barry L. Fanburg, Regina M. Day, Amy R. Simon, Sheu-Ling Lee,
and Yuichiro J. Suzuki................................................................................113
13 Reactive Oxygen Species and Cell Signaling in Lung Ischemia
Aron B. Fisher ..................................................................................................125
14 Pulmonary Vascular Barrier Regulation by Thrombin
and Edg Receptors
Jeffrey R. Jacobson and Joe G. N. Garcia ...................................................137
15 Second-Messenger Signaling in Lung Capillaries
Kaushik Parthasarathi ..................................................................................147
16 Plasma Membrane-to-Nucleus Calcium Signaling
Giles E. Hardingham ......................................................................................155
17 Signaling by Mitochondria
Navdeep S. Chandel........................................................................................167
18 Pro-Inflammatory Signaling by Endothelial Focal Complexes
in Lung
Sunita Bhattacharya......................................................................................179
19 Hydrogen Peroxide As Intracellular Messenger: Production, Target,
and Elimination
Sue Goo Rhee, Tong-Shin Chang, Yun Soo Bae, Seung-Rock Lee,
and Sang Won Kang...................................................................................191
20 Calcium-Inhibited Adenylyl Cyclase (AC ) Controls
6
Endothelial Cell Barrier Function
Troy Stevens.....................................................................................................203
Index...................................................................................................................217
Contributors
HAKAN AKCA, PhD • Walther Oncology Center, Indiana University School of
Medicine, Indianapolis, IN
YUN SOO BAE, PhD • Division of Molecular Life Sciences and Center for Cell
Signaling Research , Ewha Womans University, Seoul, Korea
ALEX BANKS • Departments of Medicine and Microbiology, College of Physicians
and Surgeons of Columbia University, New York, NY
SUNITA BHATTACHARYA, MD • Department of Pediatrics, College of Physicians and
Surgeons of Columbia University, New York, NY
NAVDEEP S. CHANDEL, PhD • Department of Medicine, Northwestern University
Medical School, Chicago, IL
TONG-SHINCHANG, PhD • Division of Molecular Life Sciences and Center for Cell
Signaling Research, Ewha Womans University, Seoul, Korea
PETER CHEN • Departments of Medicine and Microbiology, College of Physicians
and Surgeons of Columbia University, New York, NY
AUGUSTINE M. K. CHOI, MD • Department of Medicine, University of Pittsburgh
School of Medicine, Pittsburgh, PA
REGINA M. DAY,PhD • Department of Medicine, Tufts University School of
Medicine, Boston, MA
SRINIVAS DHANAKOTI, PhD • Department of Pediatrics, University of California
Los Angeles, Los Angeles, CA
DAVID B. DONNER, PhD • Walther Oncology Center, Indiana University School of
Medicine, Indianapolis, IN
BARRY L. FANBURG, MD • Department of Medicine, Tufts University School of
Medicine, Boston, MA
SCOTT FAY • Departments of Medicine and Microbiology, College of Physicians and
Surgeons of Columbia University, New York, NY
ARON B. FISHER, MD • Institute for Environmental Medicine, University of
Pennsylvania Medical Center, Philadelphia, PA
JOE G. N. GARCIA, MD • Division of Pulmonary and Critical Care Medicine, Johns
Hopkins University School of Medicine, Baltimore, MD
YUANSHENG GAO, MD • Department of Pediatrics, University of California Los
Angeles, Los Angeles, CA
JASON A. GUSTIN • Walther Oncology Center, Indiana University School of
Medicine, Indianapolis, IN
GILES E. HARDINGHAM• Department of Preclinical Veterinary Studies, Edinburgh
University, Edinburgh, UK
MARGARET M. HARNETT, PhD • Division of Immunology, University of Glasgow,
Glasgow, Scotland
ix
x Contributors
ELIZABETH O. HARRINGTON, PhD • Department of Medicine, Brown Medical School,
Providence, RI
ZHIGANG HONG, MD,PhD• Department of Medicine, VA Medical Center and
University of Minnesota, Minneapolis, MN
HARRY ISCHIROPOULOS, PhD • The Children’s Hospital of Philadelphia, The Stokes
Research Institute, and Department of Biochemistry and Biophysics, University
of Pennsylvania, Philadelphia, PA
JEFFREY R. JACOBSON, MD • Division of Pulmonary and Critical Care Medicine,
Johns Hopkins University School of Medicine, Baltimore, MD
SANG WON KANG, PhD • Division of Molecular Life Sciences and Center for Cell
Signaling Research, Ewha Womans University, Seoul, Korea
CHANDRASHEKHARK. KORGAONKAR, PhD • Walther Oncology Center, Indiana
University School of Medicine, Indianapolis, IN
WOLFGANG M. KUEBLER, MD, PhD • Institute of Physiology, Charité-
Universitaetsmedizin Berlin, Berlin, Germany
SEUNG-ROCK LEE, PhD • Division of Molecular Life Sciences and Center for Cell
Signaling Research, Ewha Womans University, Seoul, Korea
SHEU-LING LEE, PhD• Department of Medicine, Tufts University School of
Medicine, Boston, MA
JIANZE LI • Departments of Medicine and Microbiology, College of Physicians and
Surgeons of Columbia University, New York, NY
JULIE A. LOSMAN • Departments of Medicine and Microbiology, College of
Physicians and Surgeons of Columbia University, New York, NY
QING LU, PhD • Department of Medicine, Brown Medical School, Providence, RI
ASRAR B. MALIK, PhD • Department of Pharmacology, University of Illinois at
Chicago, Chicago, IL
LINDSEY D. MAYO, PhD • Indiana University School of Medicine, Indianapolis, IN
LISA MCKEAG • Departments of Medicine and Microbiology, College of Physicians
and Surgeons of Columbia University, New York, NY
DOLLY MEHTA, PhD • Department of Pharmacology, University of Illinois at
Chicago, Chicago, IL
RICHARD D. MINSHALL, PhD • Department of Pharmacology, University of Illinois at
Chicago, Chicago, IL
DANIEL P. NELSON,BS • Department of Medicine, VA Medical Center and
University of Minnesota, Minneapolis, MN
ANDREA OLSCHEWSKI • Department of Anesthesiology, Justus-Leibig University,
Giessen, Germany
OSMAN NIDAI OZES, PhD • Walther Oncology Center, Indiana University School of
Medicine, Indianapolis, IN
KAUSHIK PARTHASARATHI, PhD • Department of Physiology and Cellular Biophysics,
College of Physicians and Surgeons of Columbia University, New York, NY
ROXANA PINCHEIRA, PhD • Indiana University School of Medicine, Indianapolis, IN
USHA RAJ, MD • Department of Pediatrics, University of California Los Angeles,
Los Angeles, CA
SUE GOO RHEE, PhD • National Institute of Health, National Heart, Lung, and
Blood Institute, Bethesda, MD
Contributors xi
PAUL ROTHMAN, MD • Departments of Medicine and Microbiology, College of
Physicians and Surgeons of Columbia University, New York, NY
SHARON ROUNDS, MD • Department of Medicine, Brown Medical School,
Providence, RI
STEFAN W. RYTER • Department of Medicine, University of Pittsburgh School of
Medicine, Pittsburgh, PA
SAMI I. SAID, MD • Pulmonary and Critical Care Medicine, SUNY at Stony Brook,
Stony Brook, NY
FRED SANDER, BS • Department of Pediatrics, University of California Los Angeles,
Los Angeles, CA
AMY R. SIMON, MD • Department of Medicine, Tufts University School of Medicine,
Boston, MA
TROYSTEVENS, PhD• Department of Molecular and Cellular Pharmacology,
University of South Alabama School of Medicine, Mobile, AL
YUICHIRO J. SUZUKI, PhD • Department of Medicine, Tufts University School of
Medicine, and the USDA Human Nutrition Research Center on Aging at Tufts
University, Boston, MA
ANTHONY VARGHESE, PhD • Department of Medicine, VA Medical Center and
University of Minnesota, Minneapolis, MN
BAO Q. VUONG • Departments of Medicine and Microbiology, College of Physicians
and Surgeons of Columbia University, New York, NY
E. KENNETH WEIR, MD • Department of Medicine, VA Medical Center and
University of Minnesota, Minneapolis, MN
