Finding new receptors for serum amyloid A (P6362)

Abstract

Abstract Serum amyloid A (SAA) is a major acute-phase protein with cytokine/chemokine-like properties. It can be expressed at sites of inflammation and induce the migration of immune cells to the inflammatory sites. SAA plasma concentration can be 1000 times higher in the patients with autoimmune diseases such rheumatoid arthritis, than in the healthy people. However, its precise role in inflammation and infection remains unclear. SAA is known to bind to several receptors such as FPRL1, TLR2, and TLR4, etc. It is possible that SAA also use other chemokine receptors to recruit immune cells during the inflammation. In this study, we used a mathematical approach called Natural Vector Method (NVM) and analyzed the genetic information of all major human chemokines (total 175) and SAA. SAA was found clustered with two chemokines based on both DNA and protein sequences: CXCL9 and CCL23. We hypothesized that SAA may use these chemokines’ receptors, CXCR3 and CCR1. We found that SAA indeed can induce MAP kinase ERK activation in the receptor over-expressed cell line. We will check other receptor-mediated cell functions such as intracellular calcium mobilization, to confirm that SAA can use these two receptors. We hope that our research work not only helps to understand the function of SAA, but also introduces a new way of finding receptors for the endogenous molecules.