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Infection and Immunity, January 2003, p. 140-146, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.140-146.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Fibronectin Bound to the Surface of Staphylococcus aureus Induces Association of Very Late Antigen 5 and Intracellular Signaling Factors with Macrophage Cytoskeleton

Hitomi Shinji,* Keiko Seki, Akiko Tajima, Atsuko Uchida, and Shogo Masuda

Department of Microbiology II, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan

Received 15 April 2002/ Returned for modification 3 August 2002/ Accepted 16 October 2002

Staphylococcus aureus Cowan I and a clinically isolated coagulase-negative Staphylococcus strain, S. saprophyticus 10312, were found to have two fibronectin binding proteins, FnBPA and FnBPB. While both staphylococci bound to serum fibronectin to a similar extent, fibronectin binding significantly increased the phagocytic activity of macrophages against S. aureus (by ca. 150%) but not against S. saprophyticus. This enhancing effect of fibronectin was inhibited by an RGD sequence-containing peptide and also by anti-very late antigen 5 antibody. This suggests that the effect is mediated by very late antigen 5 expressed on macrophages. In macrophages ingesting fibronectin-bound Cowan I, {alpha}5 and ß1 chains were associated with the cytoskeleton. Cytosolic signaling factors such as paxillin, c-Src, and c-Csk were also associated with the cytoskeleton. On the contrary, ß3 integrin transiently disappeared from the cytoskeleton when macrophages ingested the fibronectin-treated S. aureus Cowan I. Furthermore, the Src kinase family tyrosine kinase Lyn dissociated from the cytoskeleton. These cellular components did not respond in a fibronectin-dependent manner when macrophages phagocytosed S. saprophyticus. This means that only fibronectin-treated S. aureus Cowan I induces the accumulation of very late antigen 5, which in turn induces the association of paxillin and tyrosine kinases. It is thought that the phagocytic activity of macrophages against fibronectin-treated S. aureus was increased by signaling via the activation of very late antigen 5.

* Corresponding author. Mailing address: Department of Microbiology II, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Phone: 81 03 (3433) 1111. Fax: 81 03 (3436) 3166. E-mail: hshinji{at}jikei.ac.jp.

Editor: V. J. DiRita

Infection and Immunity, January 2003, p. 140-146, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.140-146.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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