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Infection and Immunity, April 2007, p. 1926-1932, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.02083-05
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Evidence of Immunostimulating Lipoprotein Existing in the Natural Lipoteichoic Acid Fraction{triangledown}

Masahito Hashimoto,1 Maiko Furuyashiki,1 Ryoko Kaseya,1 Yuka Fukada,1 Mai Akimaru,1 Kazue Aoyama,2 Toshiomi Okuno,2 Toshihide Tamura,2 Teruo Kirikae,3 Fumiko Kirikae,3 Nobutaka Eiraku,4 Hirofumi Morioka,4 Yukari Fujimoto,5 Koichi Fukase,5 Katsuhiro Takashige,6 Yoichiro Moriya,6 Shoichi Kusumoto,5,{dagger} and Yasuo Suda1,2*

Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering,1 Health Service Center, Kagoshima University, Kagoshima 890-0065, Japan,4 Department of Microbiology, Hyogo College of Medicine, Hyogo 663-8501, Japan,2 Department of Infectious Diseases, International Medical Center of Japan, Tokyo 162-8655, Japan,3 Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan,5 Chugai Pharmaceutical Co., Ltd., Kanagawa 247-8530, Japan6

Received 23 December 2005/ Returned for modification 7 April 2006/ Accepted 5 January 2007

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, Pam3CSK4 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.

* Corresponding author. Mailing address: Department of Nanostructure and Advanced Materials, Kagoshima University, Korimoto 1-21-40, Kagoshima 890-0065, Japan. Phone: 81-99-285-8598. Fax: 81-99-285-3630. E-mail: ysuda{at}eng.kagoshima-u.ac.jp.

{triangledown} Published ahead of print on 5 February 2007.

Editor: J. L. Flynn

{dagger} Present address: Suntory Institute for Bioorganic Research, Osaka, Japan.

Infection and Immunity, April 2007, p. 1926-1932, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.02083-05
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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