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Infection and Immunity, September 2000, p. 5254-5260, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Soluble CD14 Enhances Membrane CD14-Mediated Responses to Peptidoglycan: Structural Requirements Differ from Those for Responses to Lipopolysaccharide

Roman Dziarski,1,* Suganya Viriyakosol,2 Theo N. Kirkland,2,3 and Dipika Gupta1

Northwest Center for Medical Education, Indiana University School of Medicine, Gary, Indiana 46408,1 and Departments of Pathology2 and Medicine,3 University of California San Diego School of Medicine, the VA San Diego Healthcare System, San Diego, California 92161

Received 27 March 2000/Returned for modification 29 May 2000/Accepted 20 June 2000

The purpose of this study was to identify the functional significance of the binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to compare the structural requirements of sCD14 for the binding to PGN and lipopolysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS-induced cell responses. sCD14 did not facilitate the responses of membrane CD14 (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the responses of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells to PGN. sCD14 enhanced mCD14-mediated cell activation by both PGN and LPS, but only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein. Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region of sCD14 were needed for binding to both PGN and LPS and for enhancement of cell activation by both PGN and LPS. However, deletions of individual sequences had different effects on the ability of sCD14 to bind to PGN and to LPS and on the ability to enhance the responses to PGN and to LPS. Thus, there are different structural requirements of sCD14 for binding to PGN and to LPS and for the enhancement of PGN- and LPS-induced cell activation.

* Corresponding author. Mailing address: Northwest Center for Medical Education, Indiana University School of Medicine, 3400 Broadway, Gary, IN 46408. Phone: (219) 980-6535. Fax: (219) 980-6566. E-mail: rdziar{at}iunhaw1.iun.indiana.edu.

Infection and Immunity, September 2000, p. 5254-5260, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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