ACTIVATION OF THE COMPLEMENT-SYSTEM BY FRANCISELLA-TULARENSIS LIPOPOLYSACCHARIDE

We have shown by combining lipopolysaccharide (LPS) extracted and puri fied from Francisella tularensis live vaccine strain (LVS) with normal complement and back titrating with sensitised sheep red blood cells t hat the LPS activates complement. Deionising the LPS and converting it into the single salt forms of pyridine, ethanolamine and triethylamin e altered the ability to activate complement according to the apparent molecular weight due to aggregation. Francisella tularensis LPS activ ated complement deficient in a component of the alternative pathway (f actor B) but failed to activate complement deficient in a component of the classical pathway (C1q). In addition normal complement suspended in ethyleneglycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic ac id (EGTA) which inactivates the classic pathway was not activated by L PS, and we concluded that the LPS activates complement predominantly v ia the classical pathway. LPS bound to specific monoclonal antibodies activated complement more than LPS alone. An anti-core monoclonal anti body was approximately tenfold more potent when bound to LPS then an a nti-O side chain monoclonal antibody in activating complement.