Comparison of cytokine-inducing activity in a lipoteichoic acid-related molecule isolated from a penicillin-killed group A Streptococcus and from untreated bacteria.
We previously generated a monoclonal antibody, TS-2, that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432, a penicillin-killed streptococcal preparation [J. Immunother. 13 (1993) 232]. Expression of the TS-2-binding antigen was markedly higher in the cell wall of the penicillin-treated Streptococcus pyogenes (OK-432) than in the untreated bacteria (Su-BBM). We here isolated the antigens from OK-432 and Su-BBM, designated OK-PSA and Su-PSA, respectively. OK-432 markedly induced IFN-gamma and interleukin (IL)-18 as compared with Su-BBM in human peripheral blood mononuclear cells (PBMC). Furthermore, all of the Thl-type and Th1-inducing cytokines tested [IFN-gamma, tumor necrosis factor (TNF)-alpha, IL-12 and IL-18] were secreted by OK-PSA-stimulated PBMC far better than by Su-PSA-treated PBMC. In addition, the cytolytic activities of the PBMC were accelerated by the stimulation with OK-432 or OK-PSA far better than by the stimulation with Su-BBM or Su-PSA. These findings strongly suggested that OK-PSA is a highly important molecule of OK-432 and may be a useful immunotherapeutic agent for the patients with malignant diseases as a potent Th inducer. It was also shown that penicillin treatment effectively enhances OK-PSA-induced anti-cancer immunity.
Okamoto
M
M
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
Oshikawa
T
T
Ohe
G
G
Furuichi
S
S
Nishikawa
H
H
Tano
T
T
Bando
T
T
Yoshida
H
H
Matsubara
S
S
Matsuno
T
T
Saito
M
M
Sato
M
M
D020170:Caspase 1 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology*; D010844:Picibanil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000737:chemistry* / Q000378:metabolism*; D013682:Teichoic Acids / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism
D003470:Culture Media; D016207:Cytokines; D017931:DNA Primers; D008070:Lipopolysaccharides; D010406:Penicillins; D012333:RNA, Messenger; D013682:Teichoic Acids; D010844:Picibanil; C009900:lipoteichoic acid; D020170:Caspase 1