[Toxicity and cytokine-inducing activity of lipopolysaccharide of virulent Yersinia pestis 231 strain].
OBJECTIVE
Determine correlation between toxicity and cytokine inducing activity of parent and conformation modified forms of lipopolysaccharides (LPS) of virulent Yersinia pestis strain.


METHODS
LPS was isolated by phenol method from Y. pestis 231 cells grown at 37 degrees C (LPS37). LPS37 was modified by "mice" toxin (MT) Y. pestis. Toxicity was controlled in mice. TNFalpha and IFNgamma cytokine production was determined by enzyme immunoassay. The study was performed in human monocytes U-937 cell line. TLR4 re-stimulation was performed after activation of monocytes by S-LPS and R-LPS of Escherichia coli.


RESULTS
LPS37 conformation change of virulent Y. pestis 231 strain during formation of complex with "mice" toxin increases its toxicity for animals by 2 times. LPS37 and LPS37-MT induce TNFalpha and IFNgamma synthesis by human monocytes. LPS37 simultaneously activates MyD88-dependent as well as MyD88-independent signal pathways. Modified LPS37-MT form is a strong activator only of MyD88-dependent pathway and thereafter induces synthesis of predominately one of the cytokines--TNFalpha. Monocyte response to primary and recurrent activation by LPS37 and LPS37-MT corresponds to R- and S-LPS E. coli cytokine response profile.


CONCLUSIONS
A direct correlation between toxicity of LPS37 and LPS37-MT and their TNFalpha-inducing activity was demonstrated in the study. LPS37 and LPS37-MT of Y. pestis 231 differentially activates TLR4 signal pathways of human monocytes.
E P
EP
Sokolova
G V
GV
Demidova
V P
VP
Ziuzina
T N
TN
Borodina
I A
IA
Bespalova
L P
LP
Alekseeva
V I
VI
Tynianova
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000737:chemistry; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015010:Yersinia pestis / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity
D001427:Bacterial Toxins; D006001:Glycoconjugates; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma