Biomaterial Database

Activation of the complement system by Francisella tularensis lipopolysaccharide. 1993

M Fulop, and T Webber, and R Manchee

Chemical and Biological Defence Establishment, Salisbury, Wilts, UK.

We have shown by combining lipopolysaccharide (LPS) extracted and purified from Francisella tularensis live vaccine strain (LVS) with normal complement and back titrating with sensitised sheep red blood cells that the LPS activates complement. Deionising the LPS and converting it into the single salt forms of pyridine, ethanolamine and triethylamine altered the ability to activate complement according to the apparent molecular weight due to aggregation. Francisella tularensis LPS activated complement deficient in a component of the alternative pathway (factor 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 acid (EGTA) which inactivates the classic pathway was not activated by LPS, and we concluded that the LPS activates complement predominantly via the classical pathway. LPS bound to specific monoclonal antibodies activated complement more than LPS alone. An anti-core monoclonal antibody was approximately tenfold more potent when bound to LPS then an anti-O side chain monoclonal antibody in activating complement.

UI	MeSH Term	Description	Entries
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D003167	Complement Activation	The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.	Activation, Complement,Activations, Complement,Complement Activations
D003170	Complement Pathway, Alternative	Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.	Alternative Complement Pathway,Properdin Pathway,Alternative Complement Activation Pathway,Complement Activation Pathway, Alternative
D003171	Complement Pathway, Classical	Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.	Classical Complement Pathway,Classical Complement Activation Pathway,Complement Activation Pathway, Classical
D005604	Francisella tularensis	The etiologic agent of TULAREMIA in man and other warm-blooded animals.	Bacterium tularense,Brucella tularensis,Francisella tularense,Pasteurella tularensis
D000907	Antibodies, Bacterial	Immunoglobulins produced in a response to BACTERIAL ANTIGENS.	Bacterial Antibodies
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal