Murine serum amyloid A3 is a high density apolipoprotein and is secreted by macrophages.

Meek, Rick L.; Eriksen, Nils; Benditt, Earl P.

doi:10.1073/pnas.89.17.7949

Cited by 145 publications

(116 citation statements)

References 32 publications

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“…4 *-49 SAA3, on the other hand, appears to be expressed primarily by tissue macrophages. 50 Our findings contrast with a previous study in which heart tissue of casein-treated mice failed to accumulate significant SAA proteins. 46 The explanation for this may be due in part to the fact that casein treatment induces an acute inflammatory response, whereas autoimmune disease in MRLJlpr mice results in chronic inflammation.…”

contrasting

confidence: 57%

“…SAA3, on the other hand, appears to be produced primarily by macrophages. 50 Using monospecific, polyclonal antisera to SAA1, SAA2, and SAA3 proteins, we observed intense positive staining in the intercellular space, capillaries, and cellular infiltrations in the myocardium of MRLJlpr mice fed the atherogenic diet ( Figures 5B and 5D). Coronary arteries that had vasculitis showed some positive staining in the intima and in cellular infiltrates.…”

Section: Immunohistochemical Studiesmentioning

confidence: 96%

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Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

Qiao¹,

Castellani²,

Fishbein³

et al. 1993

Arterioscler Thromb

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MRLJlpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRLJlpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRLJlpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRLJlpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.

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contrasting

confidence: 57%

Section: Immunohistochemical Studiesmentioning

confidence: 96%

Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

Qiao¹,

Castellani²,

Fishbein³

et al. 1993

Arterioscler Thromb

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“…SAA is encoded by a family of genes in many animals [5,6] including man [7] and rabbit [8]. Several studies of the biosynthesis of SAA have identified the hepatocyte as the primary source of this protein [9], but expression of SAA in other cells is also found [10].…”

Section: Introductionmentioning

confidence: 99%

Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits

Rygg

1996

Clinical and Experimental Immunology

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SUMMARYSerum amyloid A (SAA) is an acute-phase plasma protein which increases 100-to 1000-fold in response to inflammatory stimuli. In this study pregnant rabbits were subjected to laparotomy and their fetuses were injected with lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and scanning densitometry. In vitro derived RNA was used as standard for quantitative mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed by biological assays. Fetal rabbits responded to cytokine stimulation by increased hepatic SAA mRNA expression, both during late gestation and in the early neonatal period. However, differences in dose-responses, kinetics and mRNA concentrations were seen dependent on gestational age. IL-1 and tumour necrosis factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits corresponded with high levels in fetal, but not in maternal, serum. High levels of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult serum 1 day after a normal delivery. The study details the complexity of the cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.

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“…Proinflammatory stimuli induce SAA expression in liver; optimal expression is achieved with a combination of interleukin (IL)-1 and IL-6 (10,11). Extrahepatic synthesis of SAA by synovial fibroblasts, macrophages, adipocytes, and smooth muscle cells has been documented (12)(13)(14)(15). SAA is also expressed in atherosclerotic lesions (13,16,17).…”

mentioning

confidence: 99%

Secretory Phospholipase A2, Group IIA Is a Novel Serum Amyloid A Target Gene

Sullivan

Seidl

Rich

et al. 2010

Journal of Biological Chemistry

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Atherosclerosis is a multifactorial vascular disease characterized by formation of inflammatory lesions. Elevated circulating acute phase proteins indicate disease risk. Serum amyloid A (SAA) is one such marker but its function remains unclear. To determine the role of SAA on aortic smooth muscle cell gene expression, a preliminary screen of a number of genes was performed and a strong up-regulation of expression of secretory phospholipase A 2 , group IIA (sPLA 2 ) was identified. The SAAinduced increase in sPLA 2 was validated by real time PCR, Western blot analysis, and enzyme activity assays. Demonstrating that SAA increased expression of sPLA 2 heteronuclear RNA and that inhibiting transcription eliminated the effect of SAA on sPLA 2 mRNA suggested that the increase was transcriptional. Transient transfections and electrophoretic mobility shift assays identified CAAT enhancer-binding protein (C/EBP) and nuclear factor B (NFB) as key regulatory sites mediating the induction of sPLA 2 . Moreover, SAA activated the inhibitor of NF-B kinase (IKK) in cultured smooth muscle cells. Previous reports showed that interleukin (IL)-1␤ up-regulates Pla2g2a gene transcription via C/EBP␤ and NFB. Interestingly, SAA activated smooth muscle cell IL-1␤ mRNA expression, however, blocking IL-1 receptors had no effect on SAA-mediated activation of sPLA 2 expression. Thus, the observed changes in sPLA 2 expression were not secondary to SAA-induced IL-1 receptor activation. The association of SAA with high density lipoprotein abrogated the SAA-induced increase in sPLA 2 expression. These data suggest that during atherogenesis, SAA can amplify the involvement of smooth muscle cells in vascular inflammation and that this can lead to deposition of sPLA 2 and subsequent local changes in lipid homeostasis.Elevated circulating acute phase proteins correlate with an increased risk for atherosclerosis (1-4). One such disease indicator is serum amyloid A (SAA) 2 (5). The SAA protein family consists of 12-14-kDa constitutive (SAA 4 ) and acute phase (SAA 1 , SAA 2 , and SAA 3 ) isoforms. During inflammation, there are large changes in liver-derived plasma levels of the acute phase isoforms, SAA 1 and SAA 2 (6, 7). The other acute phase isoform, SAA 3 , is extrahepatically inducible (8), and although the locus equivalent to SAA 3 was previously believed to be a pseudogene in humans, Larson and co-workers (9) demonstrated its expression by mammary gland epithelial cells. Proinflammatory stimuli induce SAA expression in liver; optimal expression is achieved with a combination of interleukin (IL)-1 and IL-6 (10, 11). Extrahepatic synthesis of SAA by synovial fibroblasts, macrophages, adipocytes, and smooth muscle cells has been documented (12-15). SAA is also expressed in atherosclerotic lesions (13,16,17). Although several roles have been suggested, the functions of SAA remain uncertain (7). Our laboratory demonstrated that in response to IL-1␣, cultured aortic smooth muscle cells synthesize SAA (18) leading to the hypothesis that during ather...

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Murine serum amyloid A3 is a high density apolipoprotein and is secreted by macrophages.

Cited by 145 publications

References 32 publications

Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits

Secretory Phospholipase A2, Group IIA Is a Novel Serum Amyloid A Target Gene

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