Ectopeptidases

The idea to compile recent results on the ectoenzymes aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 arose from the great interest given by readers world-wide to the two proceedings volumes edited by us in 1997 and 2000 (Ansorge and Langner, 1997; Langner and Ansorge, 2000). These volumes contained the presentations at two symposia held in Magdeburg (Germany) in 1996 and 1999 under the title "Cellular peptidases in immune functions and diseases", which was also the name of the Sonderforschungsbereich in Magdeburg, sponsored by the Deutsche Forschungsgemeinschaft between 1995 and 2001. Our groups in Magdeburg and Halle during the last two decades have provided results on these two enzymes in cells of the hematopoietic system that justify a review in an edited monograph like the present one (see the reviews by Kahne et at. , 1999; Lendeckel et at. ,1999; Riemann et at. , 1999). There are, however, many other groups in Europe, US and Japan which made important contributions to this field and particularly in topics improving the understanding of physiological and pathophysiological roles ofAPN/CD13 and DPIV/CD26. Therefore we decided to invite some of them to contribute reviews of their results to this book. Having worked for about 40 years in the field of proteolysis, for both of us to see the development of activities and knowledge from protein chemistry and enzymology to physiology and pathophysiology and even to therapy is very stimulating and fascinating. Of course, this development also reflects the dramatic improvement and refinement of methods.

Klappentext

This book has a strong focus on the role APN and DPIV play in the hematopoietic system, where again signal peptides and small proteins (cytokines) are among the most interesting substrates. Additionally, both the membrane bound peptidases play roles as partners in signal transduction of lymphocytes and monocytes, and inhibition of their enzymatic activity results in cell cycle arrest, inhibition of DNA synthesis and characteristic changes of cytokine secretion pattern of T cells. This knowledge more and more is used as the base of therapeutic strategies in the treatment of a variety of inflammatory and autoimmune diseases as well as of tumors of different origin. The editors themselves with their colleagues have contributed important results about APN and DPIV that are reviewed here, and additionally, most of the leading groups in this field from Europe, U.S., Australia and Japan have contributed reviews and latest, partially unpublished results of their work.

Inhalt
1 Detection of the Activity of the Ectopeptidases DPIV and APN Using Sensitive Fluorogenic Substrates.- 2 CD13/APN in Hematopoetic Cells Expression, Function, Regulation, and Clinical Aspects.- 3 New Selective Aminopeptidase N Inhibitors as Potential Therapeutics.- 4 Physiological Roles of Ectoenzymes Indicated by the Use of Aminopeptidase Inhibitors.- 5 CD13/APN as a Target for Inhibiting Tumor Angiogenesis: A Molecular Basis for the Differential Expression of CD13/APN in Vascular Endothelium.- 6 Signal Transduction via Membrane Peptidases.- 7 The Family of CD26/DPIV and Related Ectopeptidases - The DPIV Family..- 8 CD26/DPIV in Hematopoietic Cells - Expression, Function, Regulation, Clinical Aspects.- 9 DPIV - Natural Substrates of Medical Importance.- 10 Therapeutic Strategies Exploiting DP IV inhibition - Target Disease: Type 2 Diabetes.- 11 CD26/DPIV in Diseases of the Central Nervous System.- 12 CD26/DPIV in Stress-induced, Cytokine-mediated Abortions.