Lundblad Roger L. - Proteolysis in the Interstitial Space

Proteolysis in the Interstitial Space

PROTEIN SCIENCE SERIES

SERIES EDITOR

Roger L. Lundblad

Lundblad Biotechnology

Chapel Hill, North Carolina, U.S.A.

PUBLISHED TITLES

Proteolysis in the Interstitial Space

Salvatore V. Pizzo, Roger L. Lundblad, and Monte S. Willis

Biotechnology of Plasma Proteins

Roger L. Lundblad

Chemical Modification of Biological Polymers

Roger L. Lundblad

Development and Application of Biomarkers

Roger L. Lundblad

Approaches to the Conformational Analysis of Biopharmaceuticals

Roger L. Lundblad

Application of Solution Protein Chemistry to Biotechnology

Roger L. Lundblad

Proteolysis in the Interstitial Space

Salvatore V. Pizzo

Roger L. Lundblad

Monte S. Willis

PROTEIN SCIENCE SERIES

CRC Press

Taylor & Francis Group

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2017 by Taylor & Francis Group, LLC

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Version Date: 20160517

International Standard Book Number-13: 978-1-4665-7207-2 (Hardback)

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Dedication

Salvatore V. Pizzo dedicates this work to Susan Pizzo, an author in her own right.

Roger L. Lundblad dedicates this work to Sharon Mason, the flame of the class of 57 that refuses to dim.

Monte S. Willis dedicates this book to Tina, Connor, and Declan, and their devious plots to make him happy.

Contents

The emergence of biotechnologies to foster discoveries in genomics, proteomics, and other branches of molecular biosciences has provided the potential for greater precision in medical care, from diagnostics to therapies. However, their successful application to patients has been slow for multiple reasons. The complexity of regulatory frameworks that clinical laboratory tests must adhere to and the sheer complexity of the protein and macromolecules identified as diagnostic and/or prognostic biomarkers in experimental systems account for some of these barriers. Understanding the environments in which these proteins may be assayed will be crucial, particularly where precision medicine is concerned. Thus, the concept of human extravascular fluids and bodily secretions, or more broadly interstitial fluids, is something we have grappled with for some time with increasing application in biotechnology.

Conceptually, interstitial fluids may not be as foreign as they first appear. For example, both urine and saliva are interstitial fluids commonly assayed in clinical laboratory tests. While assays for urine (a plasma ultrafiltration) and saliva (derived from glandular secretion and plasma proteins) are simple and quite basic, our further understanding of their makeup and relationship to disease in expanding biosignatures will have commercial importance in therapeutics and diagnostics. Their dynamic properties, currently viewed as static processes, are surprising. With 60% of serum albumin in the extravascular space, the dynamic movement of fluid between the intravascular and extravascular space, exchanging one entire plasma volume every 9 hours, brings to light a context in which understanding biomarkers and biomarker signatures will be needed. Similarly, understanding the dynamics of extravascular spaces derived from sources other than plasma, such as cerebral spinal fluid, will bring to light how biomarkers for specific diseases (e.g., multiple myeloma) can be created with diagnostic/therapeutic value.

This book has been organized into broad biologically relevant categories in the context of interstitial fluids. In the first half of the book, we cover the fundamental concepts of interstitial fluid. We begin by defining its composition and function ().

The coagulation system has been studied extensively in terms of diagnostics, primarily by assaying vascular spaces. However, a disconnect with this approach has always been that many of the components exist in the interstitial spaces, notably tissue factor, matrix metalloproteinases, serine protease inhibitors, and coagulation factors. The second part of this book investigates the fibrinolytic system () in the interstitial space. With increasing recognition that the interstitial environment is where many of the primary reactions of the coagulation system are playing out in the pathogenesis of disease, future assays will depend on understanding how each of these major systems contributes to the interstitial environment.

By covering a unique array of topics with a broad application to biomedical workers, including physicians and scientists in industrial and academic pursuits of biotechnology, we hope this book expands the understanding of those creating greater precision in medical care. We extend our gratitude to the many scientists that we called upon that have made substantial contributions to the literature. We hope you find our synthesis of their work a useful and valuable resource.

We wish to thank Jill Jurgensen, Barbara Norwitz, and Chuck Crumly at CRC Press/Taylor & Francis Group for their support of this work. We also acknowledge the valuable support of Ashley Rivenbark, PhD (a paid independent contractor) and Steve Conlon (Duke PhotoPath) with editing and creating, respectively, the original figures used throughout this textbook.