Format

Send to

Choose Destination
J Lipid Res. 2018 Feb;59(2):339-347. doi: 10.1194/jlr.M080887. Epub 2017 Dec 15.

Serum amyloid A3 is a high density lipoprotein-associated acute-phase protein.

Tannock LR1,2,3,4, De Beer MC2,3,5, Ji A1,2, Shridas P1,2,3, Noffsinger VP1,2, den Hartigh L6,7, Chait A6,7, De Beer FC1,2,3, Webb NR8,3,4,9.

Author information

1
Departments of Internal Medicine, University of Kentucky, Lexington, KY.
2
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY.
3
Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY.
4
Veterans Affairs Lexington, University of Kentucky, Lexington, KY.
5
Departments of Physiology, University of Kentucky, Lexington, KY.
6
Department of Medicine University of Washington, Seattle, WA.
7
University of Washington Diabetes Institute, University of Washington, Seattle, WA.
8
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY nrwebb1@uky.edu.
9
Departments of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY.

Abstract

Serum amyloid A (SAA) is a family of acute-phase reactants. Plasma levels of human SAA1/SAA2 (mouse SAA1.1/2.1) can increase ≥1,000-fold during an acute-phase response. Mice, but not humans, express a third relatively understudied SAA isoform, SAA3. We investigated whether mouse SAA3 is an HDL-associated acute-phase SAA. Quantitative RT-PCR with isoform-specific primers indicated that SAA3 and SAA1.1/2.1 are induced similarly in livers (∼2,500-fold vs. ∼6,000-fold, respectively) and fat (∼400-fold vs. ∼100-fold, respectively) of lipopolysaccharide (LPS)-injected mice. In situ hybridization demonstrated that all three SAAs are produced by hepatocytes. All three SAA isoforms were detected in plasma of LPS-injected mice, although SAA3 levels were ∼20% of SAA1.1/2.1 levels. Fast protein LC analyses indicated that virtually all of SAA1.1/2.1 eluted with HDL, whereas ∼15% of SAA3 was lipid poor/free. After density gradient ultracentrifugation, isoelectric focusing demonstrated that ∼100% of plasma SAA1.1 was recovered in HDL compared with only ∼50% of SAA2.1 and ∼10% of SAA3. Thus, SAA3 appears to be more loosely associated with HDL, resulting in lipid-poor/free SAA3. We conclude that SAA3 is a major hepatic acute-phase SAA in mice that may produce systemic effects during inflammation.

KEYWORDS:

adipose tissue; animal models; inflammation; liver

PMID:
29247043
PMCID:
PMC5794427
[Available on 2019-02-01]
DOI:
10.1194/jlr.M080887

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center