Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection.
Bottom Line: Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization, but their exact functions remain unclear.Mouse and human SAAs bound retinol with nanomolar affinity, were associated with retinol in vivo, and limited the bacterial burden in tissues after acute infection.Our results thus identify SAAs as a family of microbe-inducible retinol binding proteins, reveal a unique protein architecture involved in retinol binding, and suggest how retinol is circulated during infection.
Affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.Show MeSH
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Mentions: Initially we uncovered a relationship between SAA expression and dietary vitamin A status in mice. Microarray analysis disclosed that mice fed a vitamin A-deficient diet exhibited lower abundances of serum amyloid A (Saa) 1 and 2 transcripts in the intestine as compared to mice fed a vitamin A-replete diet (Figure 1—figure supplement 1; Table 1). Real-time quantitative PCR and immunofluorescence analysis verified that expression of small intestinal SAA1, 2, and 3 was reduced in mice fed a vitamin A-deficient diet (Figure 1A,B; Table 1). Liver expression of SAA1 and 2 was also reduced in mice fed a vitamin A-deficient diet, although the reduction in expression was less pronounced than in the intestine (Figure 1C,D). This is likely because dietary vitamin A deficiency does not completely deplete stored retinoids in the liver (Liu and Gudas, 2005). We also observed elevated expression of intestinal Saa1 and Saa2 following addition of retinol directly to the epithelial surface of small intestinal explants, and of liver Saa1 and Saa2 after intraperitoneal supplementation with retinoic acid (Figure 1—figure supplement 2). These findings support the idea that retinoids directly impact Saa expression. Addition of retinol or retinoic acid to cultured HepG2 cells (a human liver cell line) enhanced expression of SAA1 and 2 in the presence of IL-1β and IL-6 (Figure 1E,F), suggesting that the impact of dietary vitamin A on SAA expression is due to cell-intrinsic effects of retinoids. Collectively, these results show that full expression of SAAs in the intestine and liver requires dietary vitamin A.10.7554/eLife.03206.003Table 1.
Affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.