Mechanisms of Innate Immune Responses Caused by Sodium Alginate

Abstract

Alginate is a well-known naturally-derived biomaterial that has been widely used in preparing microparticles for drug delivery and in preparing scaffolds for tissue engineering. Despite desirable properties, alginate has been shown to activate inflammatory cells in vivo. The mechanisms are still unclear. In this thesis, the mechanism by which alginate caused innate immune responses was investigated in vitro by using RAW264.7 cells, a macrophage-like cell line. The NF-(kappa)B pathway, an important signaling pathway in macrophages, has been tracked to identify cellular responses. The secretion of cytokines IL-1(beta), IL-6, IL-12(p40) and TNF-(alpha) was quantified to determine the activation outcomes. Also the interaction between alginate and serum was studied. Experimental results indicated that alginate induced the activation of RAW264.7 cells with a time and dose dependent behavior. Like lipopolysaccharide, a bacterial product and known activator of innate immunity, alginate induced macrophage activation through the NF-(kappa)B pathway and eventually led to detectable IL-1(beta), IL-6 and TNF-(alpha) cytokine secretion. Serum influenced alginate recognition by macrophages in an unknown mechanism. Also, alginate promoted cell survival in a nutrition starvation condition. These results revealed in vitro alginate stimulation, and provided much information for further research.