Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human monocytes and macrophages by polyglycerolphosphate-reactive peptides.
By itself, lipoteichoic acid (LTA) obtained from S. pyogenes, S. aureus, or E. hirae poorly stimulated cytokine production by macrophages, whereas in the presence of anti-polyglycerol phosphate (PGP), the cells secreted significant amounts of IL-6. Two peptides constructed from the deduced sequence of the selected anti-PGP phage-antibody's complementary-determining region 3 of the variable heavy chain (V(H)-CDR3) reacted specifically with PGP. The monomeric form of the peptides markedly inhibited cytokine production by macrophages pretreated with LTA and anti-LTA. In contrast, the polyvalent form of biotinylated peptides complex with streptavidin-induced cytokine production by the LTA-treated macrophages. The data taken together support the concept that cross-linking of macrophage-bound LTA by anti-PGP is required for cytokine release by these cells. Importantly, these studies identified small, PGP-reactive peptides as potential tools in reducing this proinflammatory process.
Gargir
A
A
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ofek
I
I
Hasty
D
D
Meron-Sudai
S
S
Tsubery
H
H
Keisari
Y
Y
Nissim
A
A
D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D005994:Glycerophosphates / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D022801:Complementarity Determining Regions; D005994:Glycerophosphates; D007143:Immunoglobulin Heavy Chains; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019151:Peptide Library; D010455:Peptides; D013682:Teichoic Acids; C008964:polyglycerolphosphate; C009900:lipoteichoic acid