Researchers have identified the circulating protein serum amyloid P (SAP) as a natural inhibitor of fibrosis during inflammatory injury in the kidney. Using two different models of kidney injury and fibrosis in mice, researchers found that human SAP can potently inhibit fibrosis in this organ. SAP accumulated at sites of injury within the kidney, where it appeared to be associated with injured or dead cells. In the kidney, SAP acts on monocytes and macrophages, specialized white blood cells that are involved in the inflammatory response. SAP suppresses the activity of these inflammatory cells by binding to Fc-gamma receptors on their surfaces. This inhibition of cell activity is dependent on the increased production of the anti-inflammatory protein interleukin-10. SAP has previously been shown to suppress fibrosis in the lung, but through a different mechanism than that seen in the kidney. Taken together, these observations suggest that SAP may have the potential to act as a broad-based anti-fibrotic agent.
The repair of organ and tissue damage is a complex and multistep process, with an initial inflammatory response that attempts to resolve the insult coupled with wound healing and tissue remodeling. Under certain conditions, unrestrained tissue “repair” leads to the excessive deposits of fibrous scar tissue. This process, termed fibrosis, can impair organ function and, left unchecked, lead to organ failure.
This research identifies previously unknown mechanisms of action of SAP in regulating anti-inflammatory activity, and raises the possibility of using SAP or similar agents as a therapy for fibrotic kidney diseases. Subsequent testing in patients who have ongoing fibrotic diseases may determine whether the therapeutic potential seen in these mouse studies can be translated into a novel clinical intervention in patients.
Castaño AP, Lin SL, Surowy T, et al. Serum amyloid P inhibits fibrosis through Fc-gamma R-dependent monocyte-macrophage regulation in vivo. Sci Transl Med 1: 5ra13, 2009.