The Acute-Phase Protein Serum Amyloid A Induces G-CSF Expression.

Host response to injury and infection is accompanied by a rapid rise of acute-phase proteins in the blood. Serum amyloid A (SAA) is a major acute-phase protein, and has been used as a marker for inflammatory diseases. However, its precise role in inflammation has not been defined. In our previous study, we found that SAA can induce IL-8 and TNF-alpha secretion from peripheral blood neutrophils, which indicates that SAA has cytokine-like functions. We have also identified SAA as an endogenous ligand that induces the expression of interleukin-23 (IL-23), a hetero-dimeric cytokine that promotes autoimmune inflammation. In this study, we reported that SAA stimulates monocytes to secret granulocyte colony-stimulated factor (G-CSF), a cytokine and a major hematopoietic growth factor. Injection of SAA into mouse peritoneum significantly increases the number of neutrophils in both peritoneal cavity and blood circulation. These results suggest that SAA can induce granulocytosis during infection and inflammation. We hypothesize that during the inflammation, locally or systematically produced SAA can increase the number of neutrophils in blood circulation and recruits them to injured or infected sites through induction of G-CSF.