Molecular Aspects of Inflammation

288 Pages·1991·28.001 MB·English

by  K. Decker (auth.), Prof. Dr. Helmut Sies, Prof. Dr. Leopold Flohé, Prof. Dr. Guido Zimmer (eds.)

42. Colloquium der Gesellschaft fur Biologische Chemie
11.-13. April 1991 in MosbachIBaden
Molecular Aspects
of Inflammation
Edited by
H. Sies, L. Flohe and G. Zimmer
With 124 Figures
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Prof. Dr. HELMUT SIES
Institut fiir Physiologische Chemie I
Universitiit Dusseldorf
Moorenstr. 5
4000 Dusseldorf, FRG
Prof. Dr. LEOPOLD FLOIffi
Gesellschaft fUr Biotechnologische Forschung
Mascheroder Weg 1
3300 Braunschweig, FRG
Prof. Dr. GUIDO ZIMMER
Gustav-Embden-Zentrum der Biologischen Chemie
Universitiit Frankfurt
Theodor-Stern-Kai 7
6000 Frankfurt am Main, FRG
ISBN -13: 978-3-642-76414-1 e-ISBN -13 :9 78-3-642-76412 -7
DOl: 10 .1007 /978-3-642-76412-7
Library of Congress Cataloging·in-Publication Data. Molecular aspects ofinflammation: 11.-13. April 1991
in Mosbach/Baden/[42.Colloquium Mosbach 1991]. Ed. by H. Sies ... - Berlin; Heidelberg; New York;
London; Paris; Tokyo; HongKong; Barcelona; Budapest: Springer, 1991 ( ... Colloquium der Gesellschaft
fiir Biologische Chemie; 42)
ISBN-I3:978-3-642-76414-1
NE: Sies, Helmut [Hrsg.]; Colloquium Mosbach (42, 1991); Gesellschaft fiir Biologische Chemie:
... Colloquium der ...
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Preface
Understanding the molecular basis of complex biological processes has
been a major goal of biological chemistry from early on. Inflammation is
one such entity, and recent years have seen exciting progress in the under
standing of molecular interactions; there has been a long way from dolor,
rubor, calor, and tumor as a fundamental description of the phenomenon
to current knowledge, e.g., on the control of the respiratory burst of the
granulocyte, the atomic details of protease regulation, or the interaction
of cytokines.
We were glad to have been given the opportunity by the Gesellschaft
fUr Biologische Chemie to call upon experts in this bustling field of
research for this Colloquium. The sessions were organized in the order of
increasing complexity, starting with the key phenomena of the inflamma
tory response and its modulation by cytokines to intravascular events and
shock and sepsis; thus, the current attempts to apply basic knowledge on
mediators of inflammation to the clinical situation were also considered.
In-depth chapters presenting the state of the art in these areas are
collected in this book, and we thank the authors for their efforts. We also
thank the Chairmen of the sessions, Profs. C. Sorg (Munster), D. Roos
(Amsterdam), S. Bhakdi (Mainz), H. J. Muller-Eberhard (Hamburg),
H. G. Schwick (Marburg), K. Resch (Hannover), W. Schaper (Bad
Nauheim), D. Keppler (Heidelberg), and O. Trentz (Zurich) for their
input, and it is a great pleasure to acknowledge the support by Drs.
K. Beaucamp and E. Truscheit and their teams in the organization of the
Colloquium. The crisp and sunny spring weather and the beautiful
town of Mosbach did their part to make the exciting meeting as pleasant
as it was.
September 1991 HELMUT SIES, LEOPOLD FLOHE, and GUIDO ZIMMER
Contents
Basic Mechanisms of the Inflammatory Response
K. Decker ................ . 1
Neutrophils, Interleukin 8, and Related Chemotactic Cytokines
M. Baggiolini . . . . . . . . . . . . . . . . . . . . .. 25
Leukotrienes and Chemotaxis - 5-Lipoxygenase
Activation and Control
A. W. Ford-Hutchinson. . . . . . . . . . . 33
The Respiratory Burst Oxidase
B. M. Babior . . . . . . . . 41
Cellular Activation Mechanisms: The Blood Platelet as a Model
W. Siess 49
Platelet-Neutrophil Interactions
V. Ullrich, G. Hecker, and M. Schatz-Munding. 59
Proteolysis-Induced Pathomechanisms in Acute Inflammation and
Related Therapeutic Approaches
M. Jochum, W. Machleidt, and H. Fritz. . . . . . . . . . . . 73
Complement Activation
K. B. M. Reid . . . . . 93
Proteinase-Protein Inhibitor Interaction
W. Bode and R. Huber ....... . . .... 103
Attenuation of Inflammatory Disease by Reduction of
Interleukin-1 Production or Receptor Antagonism
C. A. Dinarello . . . . . . . . . . . . . . . . . . ... 117
Interleukin-6, Its Hepatic Receptor and the Acute Phase
Response of the Liver
P. C. Heinrich, G. Duiliues, S. FloM, F. Hom, E. Krause,
A. Kriittgen, L. Legres, D. Lenz, C. Liitticken, H. Schooltink,
T. Stoyan, H. S. Conradt, and S. Rose-John. . . . . . . . . . 129
VIII Contents
Transcriptional Control of Liver Acute Phase Genes by
Interleukin-6 and Leukemia Inhibitory Factor
G. Hocke, G. Baffet, Mei-Zhen Cui, T. Brechner, D. Barry,
A. Goel, R. Fletcher, C. Abney, M. Hattori, and G. H. Fey . . . 147
Disturbance of the Hemostasis and Fibrinolysis Balance by
Tumor Necrosis Factor
F. Bachmann and R. Medcalf. . . . . . . . . . . . . . . . 167
Cellular Injury by Oxidants
C. G. Cochrane ..... . ..... 177
Endothelium-Derived Relaxing Factor: Nitric Oxide
R. Busse and A. Miilsch ........... . . 189
Molecular Aspects of the Chemistry and Biology of Endotoxin
E. Th. Rietschel, T. Kirikae, W. Feist, H. Loppnow, P. Zabel,
L. Brade, A. J. Ulmer, H. Brade, U. Seydel, U. Zahringer,
M. Schlaak, H.-D. Flad, and U. Schade ............ 207
Bacterial Exotoxins and Acute Lung Failure
W. Seeger, F. Grimminger, D. Walmrath, N. Suttorp,
and S. Bhakdi. . . . . . . . . . . . . . .. . .... 233
Pathophysiological Aspects of Polyt rauma, Shock,
and Organ Failure
H. Redl, G. Schlag. . . . . . . . . . . . . . 255
Leukotrienes, Oxygen Radicals, and Cytokines in Septicemic Mice
A. Wendel, M. NiehOrster, and G. Tiegs ........... 269
Baboon Model of E. Coli Sepsis: Summary of Staging, Mechanism,
and Diagnostic Markers
F. B. Taylor Jr. . . . . . . . . . . . . . . . . . . . . . . 277
Contributors
You will find the addresses at the beginning of the respective contribution
Abney, C. 147 Krause, E. 129
Babior, B.M. 41 Kriittgen, A. 129
Bachmann, F. 167 Legres, L. 129
Baffet, G. 147 Lenz, D. 129
Baggiolini, M. 25 Loppnow, H. 207
Barry, D. 147 Liitticken, C. 129
Bhakdi, S. 233 Machleidt, W. 73
Bode, W. 103 Medcalf, R. 167
Brade, H. 207 Mei-Zhen Cui 147
Brade, L. 207 Miilsch, A. 189
Brechner, T. 147 NiehOrster, M. 269
Busse, R. 189 Redl, H. 255
Cochrane, C.G. 177 Reid, K.B.M. 93
Conradt, H.S. 129 Rietschel, E.Th. 207
Decker, K. 1 Rose-John, S. 129
Dinarello, C.A. 117 Schade, U. 207
Dufbues, G. 129 Schatz-Munding, M. 59
Feist, W. 207 Schlaak, M. 207
Fey, G.H. 147 Schlag, G. 255
Flad, H.-D. 207 Schooltink, H. 129
Fletcher, R. 147 Seeger, W. 233
FloM, S.. 129 Seydel, U. 207
Ford-Hutchinson, A.W. 33 Siess, W. 49
Fritz, H. 73 Stoyan, T. 129
Goe1, A. 147 Suttorp, N. 233
Grimminger, F. 233 Taylor, F.B. 277
Hattori, M. 147 Tiegs, G. 269
Hecker, G. 59 Ullrich, V. 59
Heinrich, P.C. 129 Ulmer, A.J. 207
Hocke, G. 147 Walmrath, D. 233
Hom, F. 129 Wendel, A. 269
Huber, R. 103 Zabel, P. 207
Jochum, M. 73 Zahringer, U. 207
Kirikae, T. 207
Basic Mechanisms of the Inflammatory Response *
K. DECKER 1
1 Introduction
Inflammation is experienced by people as a pandora box of nasty things like fever and
pain. In essence, however, it is one of the organism's most powerful emergency mea
sures designed to mobilize whatever forces can be mustered to overcome a life
threatening situation. As with many emergency actions, it sometimes happens that it
exceeds its purpose and poses by itself a grave danger to the organism. That is the
time when inflammation is just seen as a "bad", pathological process. Nevertheless, it
is basically a network of reactions indispensable for the survival of higher organisms.
In this context, inflammation shall be understood as a response elicited by injured
tissue or toxic agents (Table 1). Typical consequences are dilation and increased per
meability of blood vessels, leukocyte invasion into the afflicted areas, and loss or im
pairment of cellular functions.
Table 1. Inflammation
A response elicited by toxic agents or injured cells.
The Agents may be
microorganisms
viruses
toxins
substances released by injured cells
The Defense consists of
the reticulo-endothelial system
immunocompetent cells
the complement system
the contact activation system
The Response may involve
specific reactants
(e.g., immunoglobulins)
unspecific mechanisms
(lytic enzymes, inhibitors,
immunomodulators, mediators,
complement components, oxygen species)
Table 2. Inflammatory agents
* Dedicated to Prof. Wolfgang Oerok at the occasion of his 65th birthday
1 Biochemisches Institut der Albert-Ludwigs-Universitiit, Hermann-Herderstr. 7, D-7800
Freiburg i. Br., FRO
42 Colloquium Mosbach 1991
Molecular Aspects of Inflammation
© Springer-Verlag Berlin Heidelberg 1991
2 K. Decker
Table 2. Inflammatory agents
Microorganisms
Viruses
Bacteria
Eukaryotic parasites
Cytotoxins
Exotoxins
Endotoxins
Carrageenan
Phorbol esters
D-Galactosamine
Carbon tetrachloride
Signals from injured cells
Histamine
Nucleotides
Oligopeptides
Proteolytic enzymes
The most frequent elicitors of inflammation are of three different types (Table 2):
Microorganisms, viruses and eukaryotic parasites; toxins; cytotoxic chemicals and
substances released from cells injured by biological, chemical, or physical (mechani
cal or radiation) insults. Chemically elicited inflammations are often useful models
because they are easily and reproducibly provoked, aseptical, and more likely to be
elucidated as to their mechanisms.
Table 3. Examples of inflammatory diseases
Disease Immune component Major mediators
Immunological overreaction
Anaphylaxis, atopy IgE Histamine, eicosanoids
Lupus erythematosus IgM,lgG Multiple
Rheumatoid arthritis IgM,lgG Multiple
Granulomatosis T lymphocytes IL-4
RES-mediated disorders
Septic shock (lgE) TNF, IL-l
Asthma Histamine, leukotrienes
Adult respiratory TNF-a, eicosanoids,
distress syndrome oxygen radicals (?)
Diabetes IL-l
Proteinase-related disorders
Emphysema Elastase,
lack of aI-antitrypsin
Chronicity of inflammation
Fibrosis cirrhosis TGF-~
Basic Mechanisms of the fuflammatory Response 3
The inflammatory response of an organism involves a network of effector and tar
get cells. Their interactions may and most often do result in an inconspicuous han
dling of the damaging agent. But it may also lead to manifestation of the clinical
symptoms of inflammation described already by Galen: dolor (pain), calor (fever),
rubor (redness), and tumor (swelling). Inability to trigger a sufficiently strong in
flammatory response renders the organism compromised and open for the continued
action of the intruder. On the other hand, an excessive reaction may lead to forms of
inflammatory disease (Table 3). Thus, it is obvious that better knowledge of these
complex systems will provide new routes for pharmacological intervention.
2 Results and Discussion
2.1 Cells and Elicitors of the Inflammatory Process
Cells participating in the inflammatory response are primarily those belonging to the
reticulo-endothelial system (RES), a term. introduced by the Pathologist Ludwig
Aschoff in 1922. It includes what is now called the mononuclear phagocyte system
(MPS) (Metcalf and Burgess 1982) comprising circulating and sessile tissue macro
phages, monocytes, and natural killer (NK) cells; but also polymorphonuclear leuko
cytes (PMN, neutrophils, granulocytes), lymphocytes, mast cells (basophils), endo
thelial cells, fibroblasts, and blood platelets (thrombocytes). All of them fulfill impor
tant functions in the inflammatory response.
The subcellular and soluble components participating in the inflammatory re
sponse of the organism are of different type and origin. Some offender-specific re
sponses are mediated by the immune system, i.e., by circulating antibodies produced
by B-lymphocytes and also by T-cell-involving mechanisms. The Contact Activation
System (Cochrane and Griffin 1982) comprises parts of the coagulation systems (Fac
tors XI and XII, prekallikrein) and involves activating (often negatively charged) sur
faces of neutrophils, endothelial cells, and thrombocytes. Release of mediators, en
zymes, and reactive inorganic compounds can contribute to the spread and severity of
an inflammatory insult, e.g., in arthritis or in bacteremic shock.
2.2 Activation of Phagocytes
Phagocytes learn of the presence of noxious material by contact through receptors and
peri-or intracellular binding sites that convey the cell specificity and bring the trans
and intracellular signal transduction pathways into action. Aside from organismic of
fenders a number of activators or immunomodulators stimulate resting macrophages.
Table 4 lists some well-defmed elicitors of phagocytes. Of these agents, interferon-y ,
a product of activated lymphocytes, is the most important macrophage-activating
factor (MAF). It acts not only and not so much by itself but also as an enhancer or co
stimulator of immunomodulators like lipopolysaccharides (LPS). The concept of the
two-stage activation of phagocytes is still popular among immunologists (for review,