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.