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(Journal of Leukocyte Biology. 2001;70:537-542.)
© 2001 by Society for Leukocyte Biology

Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human monocytes and macrophages by polyglycerolphosphate-reactive peptides

Ari Gargir*, Itzhak Ofek*, David Hasty2, Shiri Meron-Sudai*, Hayim Tsubery3, Yona Keisari* and Ahuva Nissim4,||

* Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;
{dagger} Department of Anatomy and Neurobiology, University of Tennessee and Research Service (151) VAMC, Memphis;
{ddagger} Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel;
§ Bone and Joint Research Unit, St. Bartholomew’s and Royal London School of Medicine and Dentistry, Queen Mary, Charterhouse Square, United Kingdom; and
|| Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Rabin Medical Center, Belinson Campus, Petach Tikva, Israel

Correspondence: Dr. Itzhak Ofek, Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. E-mail: aofek{at}ccsg.tau.ac.il

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 (VH-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.

Key Words: LTA • PGP • phage display • Streptococci • macrophage stimulation




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