Article

Human serum amyloid A (SAA) protein: A prominent acute-phase reactant for clinical practice

Karl-Franzens University Graz, Institute of Medical Biochemistry, Austria.
European Journal of Clinical Investigation (Impact Factor: 2.83). 07/1996; 26(6):427-35. DOI: 10.1046/j.1365-2362.1996.159291.x
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Ernst Malle, Mar 08, 2014
3 Followers
 · 
111 Views
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Biochemical and Biophysical Research Communications 08/2014; 450(4). DOI:10.1016/j.bbrc.2014.07.054 · 2.28 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Placenta 06/2014; 35(8). DOI:10.1016/j.placenta.2014.05.012 · 3.29 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Placenta 01/2014; · 3.29 Impact Factor
Show more