Gangliosides can activate human alternative complement pathway

The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point of the structural similarity of LPS to ganglioside, we have investigated gangliosides which are abundantly present in animal cells for their activity on the human ACP. All of seven gangliosides tested were found to activate this pathway in a manner depending on the number of sialic acids and neutral sugars contained in the molecules. A dose - response study suggested a correlation of the threshold in ganglioside concentration with its critical micelle concentration. Gangliosides may thus serve as an intrinsic activator for ACP in animals, thereby leading to inflammation. The possibility of the participation of sialidase in complement activation is also discussed.