Widespread Expression of Serum Amyloid A in Histologically Normal Human Tissues: Predominant Localization to the Epithelium

Urieli-Shoval, Simcha; Cohen, Patrizia; Eisenberg, Shlomit; Matzner, Yaacov

doi:10.1177/002215549804601206

Cited by 197 publications

(169 citation statements)

References 31 publications

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“…This is supported by the observation by Raynes et al 19 that levels of SAA des-R reach a maximum up to 24 h later than the full-length protein. Extrahepatic expression of SAA has been shown to be widespread, including kidney epithelia 26 and more relevantly in RCC tissue by transcription profiling; 27 therefore, the detection of SAA des-RS cannot be discounted as cancer-specific and an investigation to resolve this question is underway, incorporating sera from different noncancer inflammatory conditions as well as tumors.…”

Section: Discussionmentioning

confidence: 99%

Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients

Tolson

Bogumil²,

Brunst

et al. 2004

Laboratory Investigation

184

110

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The molecular analysis of serum is an important field for the definition of potential diagnostic markers or disease-related protein alterations. Novel proteomic technologies such as the mass spectrometric-based surface-enhanced laser desorption/ionization (SELDI) ProteinChip s technique facilitate a rapid and reproducible analysis of such protein mixtures and affords the researcher a new dimension in the search for biomarkers of disease. Here, we have applied this technology to the study of a cohort of serum samples from wellcharacterized renal cell carcinoma patients for the identification of such proteins by comparison to healthy controls. We detected and characterized haptoglobin 1 a and serum amyloid a-1 (SAA-1) as disease related, in addition to an as-yet-unidentified marker of 10.84 kDa. Of particular note is the detection of multiple variants of SAA-1 in multiplex that have not been described in the sera of cancer patients. SAA-1 is detected as full-length protein, des-Arginine and des-Arginine/des-Serine variants at the N terminus by SELDI. In addition, we could also detect a low-abundant variant minus the first five N-terminal amino acids. Such variants may impact the function of the protein. We conclude the technique to be a reproducible, fast and simple mode for the discovery and analysis of marker proteins of disease in serum.

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Section: Discussionmentioning

confidence: 99%

Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients

Tolson

Bogumil²,

Brunst

et al. 2004

Laboratory Investigation

184

110

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“…Previous studies showed that SAA synthesis in the normal non-inflamed state was largely epithelial (36) and that SAA was induced in mouse intestinal epithelium in response to normal mucosal enteric bacteria (37). Thus SAA is produced in a site that needs protection against Gram-negative bacteria.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Protein Binds to Outer Membrane Protein A of Gram-negative Bacteria

Hari-Dass

Shah²,

Meyer

et al. 2005

Journal of Biological Chemistry

126

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Serum amyloid A (SAA) is the major acute phase protein in man and most mammals. We observed SAA binding to a surprisingly large number of Gram-negative bacteria, including Escherichia coli, Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae, Vibrio cholerae, and Pseudomonas aeruginosa. The binding was found to be high affinity and rapid. Importantly, this binding was not inhibited by high density lipoprotein with which SAA is normally complexed in serum. Binding was also observed when bacteria were offered serum containing SAA. Ligand blots following SDS-PAGE or two-dimensional gels revealed two major ligands of 29 and 35 kDa that bound SAA when probing with radiolabeled SAA or SAA and monoclonal anti-SAA. Following fractionation the ligand was found in the outer membrane fraction of E. coli and was identified by matrix-assisted laser desorption ionization time-offlight mass spectrometry to be outer membrane protein A (OmpA). OmpA-deficient E. coli did not bind SAA, and following purification of OmpA the protein retained binding activity. The ligands on other bacteria were likely to be homologues of OmpA because wild type, but not OprF-deficient, P. aeruginosa bound SAA.

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“…It has a multifunctional role in the pathogenesis of amyloidosis and is thought to contribute to this potentially fatal consequence of chronic inflammation (7). In atherosclerotic lesions, SAA accumulates in smooth muscle cells, monocytes/macrophages, and foam cells (3,8), and in endothelial cells on the luminal surfaces of vessels (9). SAA, mainly SAA4, an SAA only minimally affected by the acute-phase response, associates in plasma with high-density lipoprotein (HDL).…”

Section: Serum Amyloid a Induces Monocyte Tissue Factormentioning

confidence: 99%

Serum Amyloid A Induces Monocyte Tissue Factor

Cai

Song

Endoh

et al. 2007

The Journal of Immunology

107

121

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C-reactive protein (CRP) and serum amyloid A (SAA) increase in the blood of patients with inflammatory conditions and CRP-induced monocyte tissue factor (TF) may contribute to inflammation-associated thrombosis. This study demonstrates that SAA is a potent and rapid inducer of human monocyte TF. SAA induced TF mRNA in PBMC within 30 min and optimal procoagulant activity within 4 h, whereas CRP (25 μg/ml)-induced activity was minimal at this time. Unlike CRP, SAA did not synergize with LPS. Procoagulant activity was inhibited by anti-TF and was dependent on factors VII and X, and TF Ag levels were elevated on CD14+ monocytes. Responses were optimal with lymphocytes, although these were not obligatory. Inhibitor studies indicate activation of NF-κB through the ERK1/2 and p38 MAPK pathways; the cyclo-oxygenase pathway was not involved. SAA-induced TF was partially inhibited by high-density lipoprotein, but not by low-density lipoprotein or by apolipoprotein A-I. SAA is a ligand for the receptor for advanced glycation end products (RAGE), and TF generation was suppressed by ∼50% by a RAGE competitor, soluble RAGE, and by ∼85% by anti-RAGE IgG. However, another RAGE ligand, high mobility group box-1 protein, capable of inducing monocyte chemotactic protein-1 mRNA in 2 h, did not induce TF within 24 h. Cross-linking studies confirmed SAA binding to soluble RAGE. Elevated SAA is a marker of disease activity in patients with rheumatoid arthritis, and PBMC from patients with rheumatoid arthritis were more sensitive to SAA than normals, suggesting a new link between inflammation and thrombosis.

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Widespread Expression of Serum Amyloid A in Histologically Normal Human Tissues: Predominant Localization to the Epithelium

Cited by 197 publications

References 31 publications

Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients

Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients

Serum Amyloid A Protein Binds to Outer Membrane Protein A of Gram-negative Bacteria

Serum Amyloid A Induces Monocyte Tissue Factor

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