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Infection and Immunity, January 2001, p. 378-385, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.378-385.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Role of Plasma, Lipopolysaccharide-Binding Protein, and CD14 in Response of Mouse Peritoneal Exudate Macrophages to Endotoxin

Didier Heumann,1,* Yoshiyuki Adachi,2 Didier Le Roy,1 Naohito Ohno,2 Toshiro Yadomae,2 Michel Pierre Glauser,1 and Thierry Calandra1

Division of Infectious Diseases, CHUV, Lausanne, Switzerland,1 and Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science, Tokyo, Japan2

Received 20 July 2000/Returned for modification 21 September 2000/Accepted 15 October 2000

Plasma lipopolysaccharide (LPS)-binding protein (LBP) and membrane CD14 function to enhance the responses of monocytes to low concentrations of endotoxin. Surprisingly, recent reports have suggested that LBP or CD14 may be dispensable for macrophage responses to low concentrations of LPS or may even exert an inhibitory effect in the case of LBP. We therefore investigated whether LBP and CD14 participated in the response of mouse peritoneal exudate macrophages (PEM) to LPS stimulation. In the presence of a low amount of plasma (<1%) or of recombinant mouse or human LBP, PEM were found to respond to low concentrations of LPS (<5 to 10 ng/ml) in an LBP- and CD14-dependent manner. However, tumor necrosis factor production (not interleukin-6 production) by LPS-stimulated PEM was reduced when cells were stimulated in the presence of higher concentrations of plasma or serum (5 or 10%). Yet, the inhibitory effect of plasma or serum was not mediated by LBP. Taken together with previous results obtained with LBP and CD14 knockout mice in models of experimental endotoxemia, the present data confirm a critical part for LBP and CD14 in innate immune responses of both blood monocytes and tissue macrophages to endotoxins.

* Corresponding author. Mailing address: Division of Infectious Diseases, CHUV, CH-1011 Lausanne, Switzerland. Phone: 41 21 314 10 25. Fax: 41 21 314 10 36. E-mail: dheumann{at}hola.hospvd.ch.

Infection and Immunity, January 2001, p. 378-385, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.378-385.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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