Serum amyloid A induces T lymphocyte migration through chemokine receptor CXCR3

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 including T lymphocytes to the inflammatory sites. SAA plasma concentration can be 1000 times higher in patients with autoimmune diseases such rheumatoid arthritis, than in 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 our previous study, we used a mathematical approach called Natural Vector Method (NVM) to analyze the genetic information of all major human chemokines and SAA and found that chemokine receptor CXCR3 may be a new receptor for SAA. We reported here that SAA indeed can induce MAP kinase ERK activation in the CXCR3 over-expressed cell line, and trigger the receptor-mediated intracellular calcium mobilization. Our chemotaxis experiments also showed that SAA promotes CXCR3-overexpressed cell migration. These findings indicate that SAA may use lymphocyte chemokine receptor CXCR3 to recruit activated lymphocytes to the inflammation sites. We will further investigate the signaling pathways involved in the CXCR3 mediated SAA-induced cell migration. 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. [This study is supported by NSF grant DMS-1119612 and NIH grant 1SC3GM098180 awarded to Rong L He]