Acute Phase Proteins in the Acute Phase Response

ISBN-13: 9781447117414 / Angielski / Miękka / 2012 / 210 str.

Mark B. Pepys

Opis

The discovery of C-reactive protein in the laboratory of O. T. Avery at Rockefeller University in 1929-30 was the first specific obser vation of the acute phase plasma protein response (Tillett and Francis 1930). This was one of three contributions of fundamental importance which emerged from that laboratory, the other two being the recognition that polysaccharides could act as antigens and that DNA transmits genetic information. In the course of charac terization of pneumococcal carbohydrate antigens, a somatic poly saccharide common to all Rand S forms of pneumococci was identified and designated Fraction "C" (Tillet et al. 1930). Testing of sera from patients with pneumococcal infection revealed the presence of material which precipitated with the C-polysaccharide but which differed from antibody in that calcium was required for the reaction. Furthermore, the amount of reactive material was greatest when patients were acutely ill and decreased in the convalescent phase, the precise opposite of specific anti-pneumo coccal antibodies. Subsequently, the C-reactive material was shown to be a protein and to be present in the sera of individuals who were acutely ill with other, non-pneumococcal infections and tissue damaging conditions, hence Avery coined the term "acute phase" and called the protein "acute phase protein" (Abernethy and Avery 1941; MacLeod and Avery 1941). At that time methods were too insensitive to detect C-reative protein (CRP) in sera of healthy subjects and it was considered to be a pathological product.

Spis treści

1 Interleukin-1 in the Acute Phase Response.- The Acute Phase Response.- Structure of IL-1.- Synthesis and Regulation of IL-1.- IL-1 Receptor.- Pleotropic Actions of IL-1.- IL-1 and Acute Phase Reactions.- Fever.- Leukocytosis.- Acute Phase Proteins.- IL-1 and Other Cytokines.- Synergy of Action.- Induction of Other Cytokines by IL-1.- IL-1 and Corticosteroid.- In Vivo Action of IL-1.- Summary.- 2 Regulation of Human SAA Gene Expression by Cytokines.- In Vitro Expression of Human SAA.- Cis-acting Sequences Responsible for PMA Induction of SAA.- Cytokine Control of SAA Expression.- 3 Transcriptional Regulation of Acute Phase Response Genes with Emphasis on the Human C-reactive Protein Gene.- The Physiological Role of the Acute Phase Response.- Systems for the Study of the Acute Phase Response.- Monokines Responsible for the Modulation of Liver-specific Gene Expression.- Transcriptional Regulation — the Mechanism.- Liver-specific Promoters and Enhancers.- Promoters Induced During the Acute Phase.- Conclusions and Perspectives.- 4 Organization, Structure and Expression of Pentraxin Genes.- The Structure of Pentraxin Proteins.- The Structure of Pentraxin Genes.- Heat Shock Elements.- The Purine-Pyrimidine Repeat Region and Oligo-A Stretch in the CRP Intron.- The 3? Untranslated Region.- Elements Responding to Cytokines.- Genetics.- 5 ApoSSA: Structure, Tissue Expression and Possible Functions.- Background.- SAA is an Apolipoprotein.- Where are SAAs Made and Where do They go?.- Patterns of Cell and Tissue Expression of SAA mRNAs in Mice.- Rats Have SAA-related Genes.- Summary.- 6 Regulation of Biosynthesis and Secretion of Human C-reactive Protein and Serum Amyloid A.- Regulation of Biosynthesis.- Role of Cytokines.- Role of Cofactors: Signal Transduction.- Heterogeneity in the Acute Phase Response.- Regulation of CRP Secretion.- Dynamics of CRP Secretion by Rabbit.- Hepatocytes.- Subcellular Localization of the Intracellular Pool of CRP.- CRP is Specifically Retained Within the Endoplasmic Reticulum.- Conclusions.- 7 Molecular Regulation of the Acute Phase Complement Proteins.- Factor B.- The Second Component, C2.- Constitutive Expression of Factor B and C2.- Regulated Gene Expression.- Interleukin-1 and Interferon-?.- Tumor Necrosis Factor and Interleukin-6.- Summary.- 8 Biosynthesis of Acute Phase Proteins by the Liver Cells.- Role of Hepatocytes in the In Vivo Biosynthesis of APR.- Expression of APR in the Normal Unstimulated Liver.- Expression of APR During the AIR.- Role of Sinusoidal Cells in the In Vivo Biosynthesis of APR.- Summary.- 9 The Plasma Serine Protease Inhibitors (Serpins): Structural Modifications in Inflammation.- The Serpins.- Structure of the Serpins.- Synthesis of Serpins in Inflammation.- Antitrypsin.- Antitrypsin Deficiency.- The Reactive Centre.- Mechanism of Protease Inhibition.- Specificity of Inhibition.- Reactive Centre Oxidation of Antitrypsin.- The SR Conformational Change.- Physiological Significance of the SR Change.- Pathological Significance of the SR Change.- Evolutionary Loss of the SR Change.- Other Structural Modifications in Inflammation.- N-terminal Cleavage: Angiotensinogen.- Modification of Carbohydrate.- Conclusions.- 10 The Three Dimensional Structure of SAP.- 11 Structure, Metabolism and Function of Acute Phase High Density Lipoprotein.- Apo-SAA in Plasma.- Structure of Apo-SAA.- Structure of Acute Phase HDL.- Metabolic Function of Normal HDL.- Synthesis of Apo-SAA.- Plasma Clearance of Apo-SAA.- Cellular Association and Degradation of Apo-SAA.- Functions of Apo-SAA.- Concluding Remarks.- 12 Clinical Measurement of Acute Phase Proteins to Detect and Monitor Infectious Diseases.- Microbial Growth and AP Protein Response.- General Pattern of AP Protein Response in Infection.- Monitoring Disease Activity Using AP Protein Response.- AP Protein Response in Viral Infection.- Immunomodulation and AP Protein Response.- 13 C-reactive Protein: Clinical Aspects.- The Acute Phase Proteins.- The Erythrocyte Sedimentation Rate as an Indirect Indicator for the Acute Phase Reaction.- C-reactive Protein as a Direct Indicator of the Acute Phase Reaction.- Assays for CRP.- CRP Levels in Different Diseases.- Functions of CRP.- Conclusion.- 14 Pathogenesis of AA Amyloidosis.- Definition and Classification of Amyloidosis.- Serum and Tissue Amyloid A Proteins.- Structure of SAA and AA.- Induction and Production of the Acute Phase.- Protein SAA.- Apo SAA and “Apo AA”.- Displacement of SAA from HDL-SAA Complexes by Apo AI and Apo AII.- Formation and Deposition of AA Amyloid.- Incomplete Degradation of SAA.- Amyloid Enhancing Factor and Glycosaminoglycans.- Protein AP: The Amyloid “P Component”.- Summary of Some Current Hypotheses Regarding AA Amyloid Formation.- 15 Serum Amyloid P Component: A Specific Molecular Targeting Vehicle in Amyloidosis.- Serum Amyloid P Component.- Ligand Binding by SAP/AP.- Binding of SAP to Chromatin.- SAP and Amyloidosis.- Tissue Amyloid P Component.- SAP as a Targeting Vehicle in Amyloidosis.- Scintigraphic Imaging of Amyloid Deposits In Vivo.- Radiolabelled-SAP Studies in Experimental Murine Amyloidosis.- Mouse Imaging Studies Using 123I-Human SAP.- Mouse Imaging Studies Using 123I-Mouse SAP.- Localization of 125I-Pentraxins in AEF-Induced Amyloid.- 125I-SAP Localization as a Method of Quantitating Murine Amyloid Deposits.- Radiolabeled SAP Studies in Man.- Preparation of 123I-Human SAP for Clinical Studies.- Imaging of Human Amyloid Deposits.- Human SAP Turnover Studies.- Conclusions.