Evidence of immunostimulating lipoprotein existing in the natural lipoteichoic acid fraction.
Lipoteichoic acid (LTA) is a cell surface glycoconjugate of gram-positive bacteria and is reported to activate the innate immune system. We previously reported that purified LTA obtained from Enterococcus hirae has no immunostimulating activity, but a subfraction (Eh-AF) in an LTA fraction possesses activity. In this study, we established a mouse monoclonal antibody neutralizing the activity of Eh-AF and investigated its inhibitory effects. Monoclonal antibody (MAbEh1) was established by the immunization of BALB/c mice with Eh-AF, followed by hybridoma screening based on its inhibitory effect for the production of interleukin-6 (IL-6) induced by Eh-AF. MAbEh1 neutralized the production of IL-6 by LTA fraction from not only E. hirae but also Staphylococcus aureus, while it failed to block that of lipopolysaccharide, suggesting that the antibody recognized a common active structure(s) in LTA fractions. Synthetic glycolipids in these LTAs did not induce cytokine production, at least in our system. Interestingly, the antibody was found to inhibit the activity of immunostimulating synthetic lipopeptides, Pam(3)CSK(4) and FSL-1. These results suggest that MAbEh1 neutralizes the activity of lipoprotein-like compounds which is responsible for the activity of the LTA fraction of E. hirae and S. aureus.
Hashimoto
Masahito
M
Department of Nanostructure and Advanced Materials, Kagoshima University, Korimoto 1-21-40, Kagoshima 890-0065, Japan.
Furuyashiki
Maiko
M
Kaseya
Ryoko
R
Fukada
Yuka
Y
Akimaru
Mai
M
Aoyama
Kazue
K
Okuno
Toshiomi
T
Tamura
Toshihide
T
Kirikae
Teruo
T
Kirikae
Fumiko
F
Eiraku
Nobutaka
N
Morioka
Hirofumi
H
Fujimoto
Yukari
Y
Fukase
Koichi
K
Takashige
Katsuhiro
K
Moriya
Yoichiro
Y
Kusumoto
Shoichi
S
Suda
Yasuo
Y
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D045744:Cell Line, Tumor; D016983:Enterococcus / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000302:isolation & purification; D008074:Lipoproteins / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009500:Neutralization Tests; D013211:Staphylococcus aureus / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology* / Q000302:isolation & purification
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008074:Lipoproteins; D013682:Teichoic Acids; C009900:lipoteichoic acid