**Meet the editor**

Prof. Dr. Sabina Janciauskiene was born in 1960 in Sweden. Since 1992, overall objective of her research is to investigate the mechanisms controlling inflammation, with particular emphasis on the multiple roles played by serine protease inhibitors (serpins) like: alpha1-antitrypsin and alpha1-antichymotrypsin. Dr. Janciauskiene`s group was among the first to propose that serpin

misfolding can also occur due to post-translational modifications of serpin molecule, such as oxidation, nitration, interaction with other molecules and cleavage. Dr. Janciauskiene is a member of the German Lung Research Center and European Respiratory Society. She is a receiver of several prices Teggers Stipendium, King`s Gustaf V & Queen`s Victoria Award and International ALTA "B Laurell Award, for new insights in Alpha1-antitrypsin deficiency field, among others. Dr. Janciauskiene made substantial contributions through publications, book chapters, external oral/poster presentations, organizing conferences, contribution to the diagnostic test research and development, and active participation within the Leonardo Da Vinci educational program in Europe, and collaboration with Alpha1-Antitrypsin deficiency patient organizations in Sweden, Germany, and England.

Contents

**Preface VII**

Simon J. Davidson

Bicho

Witting

**Cancer: A Review 55**

**Cattle and Swine 103**

**Structure and Function 139**

Maruyama and Masaki Otagiri

**Hypothesis 163**

Mao

**High-Density Lipoprotein 77**

Chapter 1 **Immunoregulatory Properties of Acute Phase Proteins —**

Chapter 2 **Inflammation and Acute Phase Proteins in Haemostasis 31**

Chapter 3 **The Role of Haptoglobin and Its Genetic Polymorphism in**

Chapter 4 **Role of SAA in Promoting Endothelial Activation: Inhibition by**

Chapter 5 **The Use of Acute Phase Proteins as Biomarkers of Diseases in**

Csilla Tóthová, Oskar Nagy and Gabriel Kováč

Chapter 6 **Molecular Aspects of Human Alpha-1 Acid Glycoprotein —**

Kazuaki Taguchi, Koji Nishi, Victor Tuan Giam Chuang, Toru

Mikael Larsson, Tsai-Mu Cheng, Cheng-Yu Chen and Simon J. T.

Chapter 7 **Unique Assembly Structure of Human Haptoglobin Phenotypes 1-1, 2-1, and 2-2 and a Predominant Hp 1 Allele**

Maria Clara Bicho, Alda Pereira da Silva, Rui Medeiros and Manuel

Xiaosuo Wang, Xiaoping Cai, Saul Benedict Freedman and Paul K.

**Specific Focus on α1-Antitrypsin 1** S. Janciauskiene, S. Wrenger and T. Welte

## Contents

#### **Preface XI**


**Hypothesis 163** Mikael Larsson, Tsai-Mu Cheng, Cheng-Yu Chen and Simon J. T. Mao

Preface

Acute phase proteins (APPs) are a large group of proteins synthesized by the liver cells and released into the bloodstream in response to a variety of stressors as part of the acute phase of the inflammatory reaction. Proteins with a transient increase in synthesis and plasma con‐ centration are called positive, whereas proteins whose synthesis decreases are referred to as negative APPs. The synthesis of the APP is thought to be mainly regulated by inflammatory

APPs functioning as protease inhibitors, enzymes, transport proteins, coagulation proteins, and modulators of the host's immune response, and play a role in the restoration of homeo‐ stasis after injury or infection. APPs act in a time, concentration and molecular conforma‐ tion-dependent manner on a variety of cells involved in early and late stages of inflammation. APPs can directly contribute to the enhancement and/or the suppression of inflammation at different points in its evolution. The administration of specific APPs has been shown to switch the pro-inflammatory to the anti-inflammatory pathways necessary for the resolution of inflammation in vitro and in vivo. Nevertheless, the biological function of most APPs has not been totally elucidated. It is also not clear what functional advantages

Thus, the magnitude and rapidity of the changes in the specific profile of APPs, together with their short half-life, suggest a particularly important role for these proteins in the estab‐ lishment of host defense. The functional activities of specific APPs and their quantification

> **Prof. Dr. Sabina Janciauskiene** Department of Respiratory Medicine,

> > Hannover Medical School, Hannover, Germany

cytokines, such as interleukin-6, interleukin-1 and tumor necrosis factor.

may arise from the rapid changes in the blood profile of APPs as a group.

during the course of acute and chronic inflammation are discussed in this book.

## Preface

Acute phase proteins (APPs) are a large group of proteins synthesized by the liver cells and released into the bloodstream in response to a variety of stressors as part of the acute phase of the inflammatory reaction. Proteins with a transient increase in synthesis and plasma con‐ centration are called positive, whereas proteins whose synthesis decreases are referred to as negative APPs. The synthesis of the APP is thought to be mainly regulated by inflammatory cytokines, such as interleukin-6, interleukin-1 and tumor necrosis factor.

APPs functioning as protease inhibitors, enzymes, transport proteins, coagulation proteins, and modulators of the host's immune response, and play a role in the restoration of homeo‐ stasis after injury or infection. APPs act in a time, concentration and molecular conforma‐ tion-dependent manner on a variety of cells involved in early and late stages of inflammation. APPs can directly contribute to the enhancement and/or the suppression of inflammation at different points in its evolution. The administration of specific APPs has been shown to switch the pro-inflammatory to the anti-inflammatory pathways necessary for the resolution of inflammation in vitro and in vivo. Nevertheless, the biological function of most APPs has not been totally elucidated. It is also not clear what functional advantages may arise from the rapid changes in the blood profile of APPs as a group.

Thus, the magnitude and rapidity of the changes in the specific profile of APPs, together with their short half-life, suggest a particularly important role for these proteins in the estab‐ lishment of host defense. The functional activities of specific APPs and their quantification during the course of acute and chronic inflammation are discussed in this book.

> **Prof. Dr. Sabina Janciauskiene** Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany

**Chapter 1**

**Immunoregulatory Properties of Acute Phase Proteins —**

Activation of innate immune cells in response to various insults is a part of the host defence. However, if uncontrolled, this inflammatory response induces persistent hyper-expression of pro-inflammatory mediators and tissue damage. Tight control of pro-inflammatory pathways

A complex network of activating and regulatory pathways controls innate immune responses; thehepaticacute-phaseresponseisoneofthecrucialcontributorstothisregulation.Forexample, in response to infection or tissue injury within few hours the pattern of protein synthesis by the liver is drastically altered, i.e. increased expression of the so called positive acute phase pro‐ teins (APPs) like C-reactive protein (CRP), alpha1-antitrypsin (AAT) or alpha1-acid glycopro‐ tein (AGP) and decreased expression of transthyretin, retinol binding protein, cortisol binding globulin, transferrin and albumin, which represent the group of negative APPs. This produc‐ tion of APPs in hepatocytes is controlled by a variety of cytokines released during inflamma‐ tionwhereas leadingregulators are IL-1- andIL-6-type cytokineshavingadditive,inhibitory,or synergistic effects. For instance, IL-1β is shown to almost completely abrogate IL-6-induced production of α2-macroglobulin and α1-antichymotrypsin but, in contrast, to enhance produc‐ tion of CRP and serum amyloid A. No doubt, this specific regulation of AAPs expression plays

AAT, also referred to as alpha1-proteinase inhibitor or SERPINA1, is the most abundant serine protease inhibitor in human blood. AAT consists of a single polypeptide chain of 394 amino

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© 2013 Janciauskiene et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Specific Focus on α1-Antitrypsin**

S. Janciauskiene, S. Wrenger and T. Welte

http://dx.doi.org/10.5772/56393

**1. Introduction**

Additional information is available at the end of the chapter

is therefore critical for immune homeostasis and host survival.

a critical role in the regulation of the host innate immune responses.

**2. Alpha1-antitrypsin and the acute phase response**
