Gangliosides can activate human alternative complement pathway

The alternative complement pathway (ACP) in vertebrates is knownto be important in inflammatory reactions, and to be activatedby foreign substances such as bacterial lipopolysaccharide (LPS)and zymosan, although to date no intrinsic activators have beenidentified except complement receptor type 2. From the pointof the structural similarity of LPS to ganglioside, we haveinvestigated gangliosides which are abundantly present in animalcells for their activity on the human ACP. All of seven gangliosidestested were found to activate this pathway in a manner dependingon the number of sialic acids and neutral sugars contained inthe molecules. A dose - response study suggested a correlationof the threshold in ganglioside concentration with its criticalmicelle concentration. Gangliosides may thus serve as an intrinsicactivator for ACP in animals, thereby leading to inflammation.The possibility of the participation of sialidase in complementactivation is also discussed.