Malle E, De Beer FCHuman serum amyloid A (SAA) protein: a prominent acute-phase reactant for clinical practice. Eur J Clin Invest 26: 427-435

Karl-Franzens University Graz, Institute of Medical Biochemistry, Austria.
European Journal of Clinical Investigation (Impact Factor: 2.73). 07/1996; 26(6):427-35. DOI: 10.1046/j.1365-2362.1996.159291.x
Source: PubMed


Serum amyloid A (SAA) proteins comprise a family of apolipoproteins synthesized in response to cytokines released by activated monocytes/macrophages. Acute-phase protein concentrations have been advocated as objective biochemical indices of disease activity in a number of different inflammatory processes. Clinical studies in large groups of patients with a variety of disorders confirmed the rapid production and exceptionally wide dynamic range of the SAA response. It is as sensitive a marker for the acute-phase as C-reactive protein (CRP). Recent studies indicate that SAA is the most sensitive non-invasive biochemical marker for allograft rejection. Further studies comparing the measurement of SAA to CRP could reveal other indications for its specific use. These studies are now more feasible given newer assays to measure this acute-phase reactant. Observations that the acutephase response is tightly coupled to lipoprotein abnormalities and the fact that acute-SAA proteins are mainly associated with plasma lipoproteins of the high density range suggested a possible role of this apolipoprotein (apo SAA) in the development of atherosclerosis. The expression of SAA mRNA in human atherosclerotic lesions and the induction of acute-phase SAA by oxidized low-density lipoproteins strengthen the hypothesis that SAA might play a role in vascular injury and atherogenesis.

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Available from: Ernst Malle, Mar 08, 2014
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    • "The differ- 56 ent alleles of the SAA1/2 loci encode non-glycosylated acute-phase 57 SAA (A-SAA) 1/2 proteins (104-amino acids [aa], 12-kDa). A-SAA 58 may reach plasma levels 1000-fold greater than that found in the 59 non-inflammatory state, thus representing an ideal marker for 60 clinical use [5]. A-SAA acts as precursor protein for reactive 61 systemic amyloid A (AA) amyloidosis [6] and modulates the ather- 62 oprotective properties of high-density lipoproteins (HDL) during 63 inflammation [7]. "
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    ABSTRACT: The serum amyloid A (SAA) family of proteins is encoded by multiple genes, which display allelic variation and a high degree of homology in mammals. The SAA1/2 genes code for non-glycosylated acute-phase SAA1/2 proteins, that may increase up to 1000-fold during inflammation. The SAA4 gene, well characterized in humans (hSAA4) and mice (mSaa4) codes for a SAA4 protein that is glycosylated only in humans. We here report on a previously uncharacterized SAA4 gene (rSAA4) and its product in Rattus norvegicus, the only mammalian species known not to express acute-phase SAA. The exon/intron organization of rSAA4 is similar to that reported for hSAA4 and mSaa4. By performing 5′- and 3′RACE, we identified a 1830-bases containing rSAA4 mRNA (including a GA-dinucleotide tandem repeat). Highest rSAA4 mRNA expression was detected in rat liver. In McA-RH7777 rat hepatoma cells, rSAA4 transcription was significantly upregulated in response to LPS and IL-6 while IL-1α/β and TNFα were without effect. Luciferase assays with promoter-truncation constructs identified three proximal C/EBP-elements that mediate expression of rSAA4 in McA-RH7777 cells. In line with sequence prediction a 14-kDa non-glycosylated SAA4 protein is abundantly expressed in rat liver. Fluorescence microscopy revealed predominant localization of rSAA4-GFP-tagged fusion protein in the ER.
    Full-text · Article · Aug 2014 · Biochemical and Biophysical Research Communications
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    • "The serum amyloid A (SAA) family comprises lipoproteinassociated proteins, encoded by different genes with a high allelic variation [1] [2]. In humans, the non-glycosylated SAA1/2 proteins, highly induced during the acute-phase response [3], are considered as important clinical markers of inflammation [4]. While human SAA3 is a pseudogene, SAA4 codes for glycosylated SAA4 protein that represents the predominant SAA isoform under physiological conditions. "
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    ABSTRACT: Trophoblast invasion into uterine tissues represents a hallmark of first trimester placental development. As expression of serum amyloid A4 (SAA4) occurs in tumorigenic and invasive tissues we here investigated whether SAA4 is present in trophoblast-like human AC1-M59/Jeg-3 cells and trophoblast preparations of human first trimester and term placenta. SAA4 mRNA was expressed in non-stimulated and cytokine-treated AC1-M59/Jeg-3 cells. In purified trophoblast cells SAA4 mRNA expression was upregulated at weeks 10 and 12 of pregnancy. Western-blot and immunohistochemical staining of first trimester placental tissue revealed pronounced SAA4 expression in invasive trophoblast cells indicating a potential role of SAA4 during invasion.
    Full-text · Article · Jun 2014 · Placenta
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    • "The primers used for amplification are described in Table 1. Because human SAA protein consists of 3 tightly linked genes (SAA1, SAA2 and SAA4) [17], the GenBank database from the National Center for Biotechnology Information (NCBI) was consulted, and portions of the genes that were not in the homology region were selected. These primers were then synthesized ad hoc by an external company (Sigma-Aldrich). "
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    ABSTRACT: Background Chronic systemic inflammatory syndrome has been implicated in the pathobiology of extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). We aimed to investigate which cell types within lung tissue are responsible for expressing major acute-phase reactants in COPD patients and disease-free (“resistant”) smokers. Methods An observational case–control study was performed to investigate three different cell types in surgical lung samples of COPD patients and resistant smokers via expression of the C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) genes. Epithelial cells, macrophages and fibroblasts from the lung parenchyma were separated by magnetic microbeads (CD326, CD14 and anti-fibroblast), and gene expression was evaluated by RT-PCR. Results The sample consisted of 74 subjects, including 40 COPD patients and 34 smokers without disease. All three cell types were capable of synthesizing these biomarkers to some extent. In fibroblasts, gene expression analysis of the studied biomarkers demonstrated increased SAA2 and decreased SAA1 in patients with COPD. In epithelial cells, there was a marked increase in CRP, which was not observed in fibroblasts or macrophages. In macrophages, however, gene expression of these markers was decreased in COPD patients compared to controls. Conclusions These results provide novel information regarding the gene expression of CRP and SAA in different cell types in the lung parenchyma. This study revealed differences in the expression of these markers according to cell type and disease status and contributes to the identification of cell types that are responsible for the secretion of these molecules.
    Full-text · Article · May 2014 · BMC Pulmonary Medicine
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