SAA-only HDL formed during the acute phase response in apoA-I+/+ and apoA-I-/- mice.

Department of Pathology, the University of Chicago, Chicago, IL 60637, USA.
The Journal of Lipid Research (Impact Factor: 4.73). 06/1999; 40(6):1090-103.
Source: PubMed

ABSTRACT Serum amyloid A (SAA) is an acute phase protein of unknown function that is involved in systemic amyloidosis and may also be involved in atherogenesis. The precise role of SAA in these processes has not been established. SAA circulates in plasma bound to high density lipoprotein-3 (HDL3). The pathway for the production of SAA-containing HDL is not known. To test whether apolipoprotein (apo)A-I-HDL is required in the production of SAA-HDL, we analyzed the lipopolysaccharide (LPS)-induced changes in apoA-I+/+ and apoA-I-/- mice. In apoA-I+/+ mice, after injection of LPS, remodeling of HDL occurred: total cholesterol increased and apoA-I decreased slightly and shifted to lighter density. Dense (density of HDL3) but large (size of HDL2 ) SAA-containing particles were formed. Upon fast phase liquid chromatography fractionation of plasma, >90% of SAA eluted with HDL that was enriched in cholesterol and phospholipid and shifted "leftward" to larger particles. Non-denaturing immunoprecipitation with anti-mouse apoA-I precipitated all of the apoA-I but not all of the SAA, confirming the presence of SAA-HDL devoid of apoA-I. In the apoA-I-/- mice, which normally have very low plasma lipid levels, LPS injection resulted in significantly increased total and HDL cholesterol. Greater than 90% of the SAA was lipid associated and was found on dense but large, spherical HDL particles essentially devoid of other apolipoproteins.We conclude that serum amyloid A (SAA) is able to sequester lipid, forming dense but large HDL particles with or without apoA-I or other apolipoproteins. The capacity to isolate lipoprotein particles containing SAA as the predominant or only apolipoprotein provides an important system to further explore the biological function of SAA.

  • [Show abstract] [Hide abstract]
    ABSTRACT: This study investigated the effects of repeated oronasal treatment with lipopolysaccharide (LPS) on the humoral immune responses in saliva, vaginal mucus, and the plasma markers of the acute phase response in periparturient dairy cows. One hundred pregnant Holstein cows were administered either 3 increasing doses of LPS (n = 50) as follows: 1) 0.01 µg/kg body weight (BW) on d -28, 2) 0.05 µg/kg BW on d -25, and -21, and 3) 0.1 µg/kg BW on d -18, and -14, or sterile saline solution (controls; n = 50) oronasally for 3 consecutive wk starting at 28 d before parturition. Intensive sampling was conducted on thirty cows (n = 15/group). Multiple saliva, vaginal mucus and blood samples were collected around parturition and analyzed for total immunoglobulin-(Ig)A, plasma serum amyloid A (SAA), lipopolysaccharide-binding protein (LBP), anti-LPS IgA, IgG, IgM, tumour necrosis factor(TNF)-α, and interleukin(IL)-1. Results regarding total secretory IgA (sIgA) antibodies showed greater concentrations in the saliva and an overall tendency for higher total sIgA in the vaginal mucus of the LPS-treated cows. Treatment had no effect on plasma sIgA, IgG, IgM anti-LPS antibodies, haptoglobin, SAA, LBP, TNF-α, and IL-1. Treatments by time interactions were observed for SAA and IL-1 with lowered concentrations of both variables in the plasma of LPS-treated cows after parturition. Overall, repeated oronasal LPS treatment clearly enhanced total sIgA antibodies in the saliva, stimulated their production in vaginal mucus shortly before calving, and lowered plasma IL-1 around parturition, but showed limited effects on markers of the acute phase response in the plasma in dairy cows around parturition.
    PLoS ONE 07/2014; 9(7):e103504. DOI:10.1371/journal.pone.0103504 · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prospective studies of cardiovascular risk-factors have shown that reduced plasma levels of HDL-cholesterol are associated with increased risk of coronary-disease. Experimental and translational studies have revealed several potential anti-atherogenic effects of HDL, including protective effects of HDL on endothelial cell functions. HDL has been suggested to protect endothelial cell functions by preventing oxidation of LDL and its adverse endothelial effects. Moreover, HDL from healthy subjects can directly stimulate endothelial cell production of nitric-oxide, anti-inflammatory, anti-apoptotic, anti-thrombotic effects, and endothelial-repair processes. Recent clinical-trials using HDL-cholesterol raising agents, such as torcetrapib, dalcetrapib and niacin, could not observe significant reduction of cardiovascular events in patients with coronary-disease. Growing evidence suggests that vascular effects of HDL are highly heterogenous and vasoprotective properties of HDL are altered in patients with coronary-disease. Notably, in recent studies no clear association of higher HDL-cholesterol levels with reduced risk of cardiovascular events was observed in patients with established coronary-disease. Greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore crucial within the context of HDL-targeted therapies. In this review, we will address different effects of HDL on endothelial cell functions potentially relevant to atherosclerotic vascular disease and explore molecular mechanisms leading to dysfunctional HDL.
    The Journal of Lipid Research 07/2013; 54(12). DOI:10.1194/jlr.R037762 · 4.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
    Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 06/2014; 6(6). DOI:10.1002/wnan.1279 · 4.24 Impact Factor

Full-text (2 Sources)

Available from
Jun 5, 2014