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: To test whether SAAs also associate with retinol in vivo, we sought to purify SAAs from mouse tissues and assay for the presence of associated retinol. SAAs were difficult to purify from the mouse intestine due to the presence of large amounts of contaminating protein, even under conditions where expression of SAAs was maximally induced. However, SAAs constitute a high proportion of serum protein during acute systemic infection (McAdam and Sipe, 1976; Zhang et al., 2005). We were therefore able to use size exclusion chromatography to recover a SAA-enriched fraction from the sera of mice infected intraperitoneally with Salmonella typhimurium for 24 hr (Figure 3—figure supplement 1A–C). Mass spectrometry revealed that the SAA-enriched protein fraction was devoid of other known retinol binding proteins (Figure 3—figure supplement 1D). Liquid chromatography tandem mass spectrometry (LC-MS/MS) indicated the presence of retinol in the SAA-enriched fraction (Figure 3, Figure 3—figure supplement 2A–C) in a molar ratio of ∼1 mol retinol/4 mol SAA (Figure 3, inset). In these analyses, retinoic acid was not detected, and retinol was not detected in the equivalent serum fraction recovered from Saa1/2−/− mice (Eckhardt et al., 2010) (Figure 3), suggesting that the retinol was preferentially associated with SAA.10.7554/eLife.03206.010Figure 3.Serum SAA is associated with retinol in vivo.
Affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.