Low molecular weight polysialic acid binds to properdin and reduces the activity of the alternative complement pathway.

Sialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with complement activation, but the exact molecular mechanism is still unclear. Here, we show that soluble polySia avDP20 (molecular weight of ~ 6 kDa) reduced the binding of serum-derived alternative pathway complement activator properdin to the cell surface of lesioned Hepa-1c1c7 and PC-12 neuroblastoma cells. Furthermore, polySia avDP20 added to human serum blocked the alternative complement pathway triggered by plate-bound lipopolysaccharides. Interestingly, no inhibitory effect was observed with monosialic acid or oligosialic acid with a chain length of DP3 and DP5. In addition, polySia avDP20 directly bound properdin, but not complement factor H. These data show that soluble polySia avDP20 binds properdin and reduces the alternative complement pathway activity. Results strengthen the previously described concept of self-recognition of sialylation as check-point control of complement activation in innate immunity.