Table Of ContentCELLULAR PEPTIDASES
IN IMMUNE
FUNCTIONS AND
DISEASES 2
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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CELLULAR PEPTIDASES
IN IMMUNE
FUNCTIONS AND
DISEASES 2
Edited by
Jürgen Langner
Martin Luther University
Halle, Germany
and
Siegfried Ansorge
Otto von Guericke University
Magdeburg, Germany
Kluwer Academic Publishers
New York, Boston, Dordrecht, London, Moscow
eBookISBN: 0-306-46826-3
Print ISBN: 0-306-46383-0
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PREFACE
The good response and high scientific output of the first meeting in 1996 encouraged us
tocontinuewithasecondone, “CellularpeptidasesinImmuneFunctionsandDiseases
(II)” which was held September 12–14th, 1999 again at Magdeburg-Herrenkrug,
Germany. This meeting again was organised by the Sonderforschungsbereich 387 of
the Deutsche Forschungsgemeinschaft “Zelluläre Proteasen, Bedeutung für Immun-
mechanismen undentzündliche Erkrankungen”.Thisfieldhasexpandedcontinuously
and has become anestablishedandhighlyeffectiveareaduring thelastyears.Sincethe
first meeting in 1996 new proteases have been detected and new topics have been
explored whereproteolysisplays animportantrole. Increasingly itis becomingclear
thatmany—if notall—pathomechanisms ofinfectious and inflammatory diseases and
malignancies are closely associated with dysregulation of proteolytic enzymes. The
activeparticipation ofcolleagues from abouttwenty laboratoriesinGermany andfrom
other European countries—in addition to the invited speakers—provides telling evi-
dence of the attraction of this field, also outside the SFB.
The present volume contains most of the presentations of the invited speakers.
The three parts of the contents each are introduced by a review of the topic of the
respective section. Weunderstand this asahelpfulintroduction forthose readerswho
are not so close to the special topics of proteolysis in relation to immune functions
covered by the meeting. In addition, short communications are included from the
members of the SFB showing the variety of projects as well as their development.
Included are also some contribution from participants of groups outside the SFB,
originally presented as posters.
We are glad to have again the opportunity to publish this volume in the series
“Advances in Experimental Medicine and Biology” of Kluwer Academic/Plenum
Publishers, and we are especially grateful to Joanna Lawrence, London, for her
invaluable help and all cooperation in the production of this book.
Financial support of the meeting was provided by the Deutsche Forschungs-
gemeinschaft, the Ministerium für Kultur des Landes Sachsen-Anhalt, Otto-von-
Guericke-Universität Magdeburg, Martin-Luther-Universität Halle-Wittenberg and
the companies: Becton Dickinson GmbH Heidelberg, Biochrom Beteiligungs GmbH
& Co, Centeon/Liederbach, Karl Roth GmbH & Co KG, NEN Life Science Products
GmbH, R & D Systems, Röche Diagnostics GmbH.
v
vi Preface
The organization of the meeting was greatly managed by Gudrun Plexnies and
Barbara Schotte. The editorial work was excellently performed by Christi Walcker.
Invaluable help with all editorial computer problems was provided by Cornelius
Hempel. Our deep gratitude goes to all of them.
Jürgen Langner
Siegfried Ansorge
CONTENTS
Part I: Membrane Ectopeptidases with Influence on Immune Functions
1. Review: The Role ofMembrane Peptidases in Immune Functions ..... 1
Uwe Lendeckel, Thilo Kähne, Dagmar Riemann, Klaus Neubert,
Marco Arndt, and Dirk Reinhold
2. Structure and Function of Aminopeptidase N .................. 25
Hans Sjöström, Ove Norén, and Olsen
3. Modulation of WNT-5a Expression by Actinonin: Linkage of APN
to the WNT-Pathway? ......................................... 35
Uwe Lendeckel, Marco Arndt, Karin Frank, Antje Spiess,
Dirk Reinhold, and Siegfried Ansorge
4. Enzymatic Activity is not a Precondition for the Intracellular Calcium
Increase Mediated by mAbs Specific for Aminopeptidase N/CD13 ..... 43
Alexander Navarrete Santos, Jürgen Langner, and Dagmar Riemann
5. Transforming Growth Factor- Increases the Expression
of Aminopeptidase N/CD13 mRNA and Protein in Monocytes
and Monocytic Cell Lines ...................................... 49
Astrid Kehlen, Jürgen Langner, and Dagmar Riemann
6. Cell-Cell Contact Between Lymphocytes and Fibroblast-like
Synoviocytes Induces Lymphocytic Expression of Aminopeptidase
N/CD13 and Results in Lymphocytic Activation ................... 57
Dagmar Riemann, Jana Röntsch, Bettina Hause, Jürgen Langner,
and Astrid Kehlen
7. Natural Substrates of Dipeptidyl Peptidase IV ..................... 67
Ingrid De Meester, Christine Durinx, Günther Bal, Paul Proost,
Sofie Struyf, Filip Goossens, Koen Augustyns, and Simon Schärpe
vii
viii Contents
8. Relating Structure to Function in the Beta-Propeller Domain of
Dipeptidyl Peptidase IV: Point Mutations that Influence Adenosine
Deaminase Binding, Antibody Binding and Enzyme Activity ......... 89
Mark D. Gorrell, Catherine A. Abbott, Thilo Kähne, Miriam T. Levy,
W. Bret Church, and Geoffrey W. McCaughan
9. Development of a Tertiary-Structure Model of the C-Terminal Domain
of DPP IV .................................................. 97
Wolfgang Brandt
10. Post Proline Cleaving Peptidases Having DP IV Like Enzyme Activity:
Post-Proline Peptidases ........................................ 103
Catherine A. Abbott, Denise Yu, Geoffrey W. McCaughan,
and Mark D. Gorrell
11. A New Type of Fluorogenic Substrates for Determination of Cellular
Dipeptidyl Peptidase IV (DP IV/CD26) Activity . . . . . . . . . . . . . . . . . . 111
Susan Lorey, Jürgen Faust, Frank Bühling, Siegfried Ansorge,
and Klaus Neubert
12. Potent Inhibitors of Dipeptidyl Peptidase IV and their Mechanisms
of Inhibition ................................................. 117
Angela Stöckel-Maschek, Beate Stiebitz, Ilona Born, Jürgen Faust,
Werner Mögelin, and Klaus Neubert
13. N-terminal HIV-1 TAT Nonapeptides as Inhibitors of Dipeptidyl
Peptidase IV. Conformational Characterization ..................... 125
Carmen Mrestani-Klaus, Annett Fengler, Jürgen Faust,
Wolfgang Brandt, Sabine Wrenger, Dirk Reinhold, Siegfried Ansorge,
and Klaus Neubert
14. Signal Transduction Events Induced or Affected by Inhibition of
the Catalytic Activity of Dipeptidyl Peptidase IV (DP IV, CD26) ...... 131
Thilo Kähne, Dirk Reinhold, Klaus Neubert, Ilona Born, Jürgen Faust,
and Siegfried Ansorge
15. Specific Inhibitors of Dipeptidyl Peptidase IV Suppress mRNA
Expression of DP IV/CD26 and Cytokines ........................ 139
Marco Arndt, Dirk Reinhold, Uwe Lendeckel, Antje Spiess,
Jürgen Faust, Klaus Neubert, and Siegfried Ansorge
16. Dipeptidyl Peptidase IV in Inflammatory CNS Disease .............. 145
Andreas Steinbrecher, Dirk Reinhold, Laura Quigley, Ameer Gado,
Nancy Tresser, Leonid Izikson, Ilona Born, Jürgen Faust,
Klaus Neubert, Roland Martin, Siegfried Ansorge, and Stefan Brocke
Contents ix
17. Dipeptidyl PeptidaseIV (CD26): Role in T CellActivation and
Autoimmune Disease ......................................... 155
Dirk Reinhold, Bernhard Hemmer, Bruno Gran, Andreas Steinbrecher,
Stefan Brocke, Thilo Kähne, Sabine Wrenger, Ilona Born, Jürgen Faust,
Klaus Neubert, Roland Martin, and Siegfried Ansorge
18. Effects of Nonapeptides Derived from the N-Terminal Structure
of Human Immunodeficiency Virus-1 (HIV-1) TAT on Suppression
of CD26-Dependent T Cell Growth .............................. 161
Sabine Wrenger, Dirk Reinhold, Jürgen Faust, Carmen Mrestani-Klaus,
Wolfgang Brandt, Annen Fengler, Klaus Neubert, and Siegfried Ansorge
19. DNA Synthesis in Cultured Human Keratinocytes and HACAT
Keratinocytes is Reduced by Specific Inhibition of Dipeptidyl Peptidase
IV (CD26) Enzymatic Activity .................................. 167
Robert Vetter, Dirk Reinhold, Frank Bühling, Uwe Lendeckel,
Ilona Born, Jürgen Faust, Klaus Neubert, Siegfried Ansorge,
and Harald Gollnick
20. Attractin: A CUB-Family Protease Involved in T Cell-Monocyte/
Macrophage Interactions ....................................... 173
Jonathan S. Duke-Cohan, Wen Tang, and Stuart F. Schlossman
21. Analogs of Glucose-Dependent Insulinotropic Polypeptide with
Increased Dipeptidyl Peptidase IV Resistance ...................... 187
Kerstin Kühn-Wache, Susanne Manhart, Torsten Hoffmann,
Simon A. Hinke, R. Gelling, Raymond A. Pederson,
Christopher H.S. McIntosh, and Hans-Ullrich Demuth
22. Dipeptidyl Peptidase IV (DPP IV, CD26) in Patients with Mental Eating
Disorders ................................................... 197
Martin Hildebrandt, Matthias Rose, Christine May r, Petra Arck,
Cora Schüler, Werner Reutter, Abdulgabar Salama,
and Burghard F. Klapp
23. The Membrane-Bound Ectopeptidase CPM as a Marker of Macrophage
Maturation in Vitro and in Vivo ................................. 205
Michael Rehli, Stefan W. Krause, and Reinhard Andreesen
24. Matrix Metalloproteinases (MMP-8, -13, and -14) Interact with
the Clotting System and Degrade Fibrinogen and Factor XII (Hagemann
Factor) ..................................................... 217
Harald Tschesche, Andrea Lichte, Oliver Hiller, André Oberpichler,
Frank H. Büttner, and Eckart Bartnik
x Contents
25. The Neprilysin Family in Health and Disease ...................... 229
Anthony J. Turner, Carolyn D. Brown, Julie A. Carson, and Kay Barnes
Part II: Cellular Endopeptidases:
New Cathepsins; Results from Knock-out-mice; Regulatory Aspects
26. Review: Novel Cysteine Proteases of the Papain Family ............. 241
Frank Bühling, Annen Fengler, Wolfgang Brandt, Tobias Welte,
Siegfried Ansorge, and Dorit K. Nägler
27. Development and Validation of Homology Models of Human
Cathepsins K, S, H, and F ..................................... 255
Annett Fengler and Wolfgang Brandt
28. The Function of Propeptide Domains ofCysteine Proteinases ......... 261
Bernd Wiederanders
29. Human Cathepsins W and F Form a New Subgroup of Cathepsins that
is Evolutionarily Separated from the Cathepsin B- and L-like Cysteine
Proteases ................................................... 271
Thomas Wex, Brynn Levy, Heike Wex, and Dieter Brömme
30. Cathepsin K Expression in Human Lung .......................... 281
Frank Bühling, Nadine Waldburg, Annegret Gerber, Carsten Häckel,
Sabine Krüger, Dirk Reinhold, Dieter Brömme, Ekkehard Weber,
Siegfried Ansorge, and Tobias Weite
31. Expression of Cathepsins B and L in Human Lung Epithelial Cells
is Regulated by Cytokines ..................................... 287
Annegret Gerber, Tobias Weite, Siegfried Ansorge, and Frank Bühling
32. Functions of Cathepsin K in Bone Resorption: Lessons from Cathepsin
K Deficient Mice .............................................. 293
Paul Saftig, Ernst Hunziker, Vincent Everts, Sheila Jones, Alan Boyde,
Olaf Wehmeyer, Anke Sute r, and Kurt von Figura
33. Ceramide as an Activator Lipid of Cathepsin D .................... 305
Michael Heinrich, Marc Wickel, Supandi Winoto-Morbach,
Wulf Schneider-Brachen, Thomas Weber, Josef Brunner, Paul Saftig,
Christoph Peters, Martin Krönke, and Stefan Schütze
34. Human Cathepsin X: A Novel Cysteine Protease with Unique
Specificity ................................................... 317
Robert Ménard, Dorit K. Nägler, Rulin Zhang, Wendy Tam,
Traian Sulea, andEnrico O. Purisima
