Aminopeptidase N (APN)/CD13 and dipeptidylpeptidase IV (DPIV)/CD26 are proteolytic enzymes with ubiquitous occurrence in the body of animals and men. Their physiological roles depend on the respective location: in gut and kidney tubules degradation of smaller proteins and peptides serves in absorption of nutrients or reabsorption of amino acids from urine. In the CNS their important substrates are biologically active peptides (e.g. enkephalins). This book, however, 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the leading groups in this field from Europe, U.S., Australia and Japan have contributed reviews and latest, partially unpublished results of their work. Researchers of many fields of biosciences and medicine will find interesting reading in the book and new impulse for basic research as well as for clinical applications.

Of the many special roles played by proteolytic enzymes in immune reactions, this study addresses different aspects of membrane peptidases, signal transduction via ligation of membrane peptidases (especially of dipeptidyl peptidase IV/CD26 and aminopeptidase N/CD13), and regulation of membrane peptidases in vivo and in vitro. A number of newly discovered peptidases (including cathepsin F, W and X, carboxypeptidase X, attractin) are described, with special emphasis given to the role of peptidases in immune and defense reactions and in the pathogenesis of inflammatory and other diseases, including rheumatoid arthritis, pancreatitis, multiple sclerosis, Alzheimer's disease and tumours of various origins. The focus on the involvement of a selection of proteolytic enzymes in immune reactions and diseases is a useful feature of this multifaceted work , which combines biochemical, immunological and clinical research reports with literary reviews of the field.

This book stems from a conference held at Magdeburg-Herrenkrug, Germany, in November 1996 on "Cellular Peptidases in Immune Functions and Diseases. " This sympo- sium was designed to bring together scientists from diverse areas of expertise to discuss issues of newly identified relevance of proteolytic processes and their role as molecular regulators in the immune system and in diseases. The meeting was organized by the Son- derforschungsbereich 387 of the Deutsche Forschungsgemeinschaft "ZelluHire Proteasen, Bedeutung fiir Immunmechanismen und entziindliche Erkrankungen," which links re- search groups from the Otto von Guericke University Magdeburg and the Martin Luther University Halle. It has become clear during the last decade that proteolysis, the processing and degrada- tion of peptides and proteins, has to be considered as a special level of epigenetic control of practically all processes of life and-an understanding dating from the last three years or so--also of cell death or apoptosis. There is also increasing evidence that proteolysis does play a crucial role in all areas of immune functions as well as in inflammatory and neoplastic diseases. Cellular proteases have central functions in natural (nonspecific) as well as acquired in the cognitive phase (antigen processing and presen- (specific) immunity. They are involved tation), in the activation phase (e. g. , generation and processing of cytokines, function of CD26, CD 13, processing of transcription factors) as well as in the effector phase of the im- mune response (e. g. , complement system, granzymes, elastase, proteinase 3.

Of the many special roles played by proteolytic enzymes in immune reactions, this book addresses different aspects of membrane peptidases, signal transduction via ligation of membrane peptidases (especially of dipeptidyl peptidase IV/CD26 and aminopeptidase N/CD13), and regulation of membrane peptidases in vivo and in vitro. A number of newly discovered peptidases (including cathepsin F, W and X, carboxypeptidase X, attractin) are described, with special emphasis given to the role of peptidases in immune and defense reactions and in the pathogenesis of inflammatory and other diseases, including rheumatoid arthritis, pancreatitis, multiple sclerosis, Alzheimer's disease and tumours of various origins. The focus on the involvement of a selection of proteolytic enzymes in immune reactions and diseases is a unique feature of this multifaceted work , which combines biochemical, immunological and clinical research reports with literary reviews of the field.

This book stems from a conference held at Magdeburg-Herrenkrug, Germany, in November 1996 on "Cellular Peptidases in Immune Functions and Diseases. " This sympo- sium was designed to bring together scientists from diverse areas of expertise to discuss issues of newly identified relevance of proteolytic processes and their role as molecular regulators in the immune system and in diseases. The meeting was organized by the Son- derforschungsbereich 387 of the Deutsche Forschungsgemeinschaft "ZelluHire Proteasen, Bedeutung fiir Immunmechanismen und entziindliche Erkrankungen," which links re- search groups from the Otto von Guericke University Magdeburg and the Martin Luther University Halle. It has become clear during the last decade that proteolysis, the processing and degrada- tion of peptides and proteins, has to be considered as a special level of epigenetic control of practically all processes of life and-an understanding dating from the last three years or so--also of cell death or apoptosis. There is also increasing evidence that proteolysis does play a crucial role in all areas of immune functions as well as in inflammatory and neoplastic diseases. Cellular proteases have central functions in natural (nonspecific) as well as acquired in the cognitive phase (antigen processing and presen- (specific) immunity. They are involved tation), in the activation phase (e. g. , generation and processing of cytokines, function of CD26, CD 13, processing of transcription factors) as well as in the effector phase of the im- mune response (e. g. , complement system, granzymes, elastase, proteinase 3.

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.