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Infection and Immunity, September 1999, p. 4485-4489, Vol. 67, No. 9
Department of Microbiology and Immunology,
Weill Medical College of Cornell University, New York, New York
10021,1 and Merck Research Laboratories,
Rahway, New Jersey 070652
Received 2 March 1999/Returned for modification 11 May
1999/Accepted 23 June 1999
Macrophages are among the most sensitive targets of bacterial
endotoxin (LPS), responding to minute amounts of LPS by releasing a
battery of inflammatory mediators. Transfection of macrophages with
secretory leukocyte protease inhibitor (SLPI) renders these cells
refractory to LPS stimulation. Here we show that uptake of LPS from
soluble CD14 (sCD14)-LPS complexes by SLPI-overexpressing cells was
only 50% of that seen in control cells. SLPI transfectants and mock
transfectants did not differ in the surface expression of CD14 or CD18.
We show, in addition, that recombinant human SLPI can bind to purified
endotoxin in vitro. SLPI caused a decrease in the binding of LPS to
sCD14 as assessed both by fluorescence quenching of labeled LPS and by
nondenaturing polyacrylamide gel electrophoresis. These results suggest
that the inhibitory effect of SLPI on macrophage responses to LPS may,
in part, be due to its blockade of LPS transfer to soluble CD14 and its
interference with uptake of LPS from LPS-sCD14 complexes by macrophages.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Secretory Leukocyte Protease Inhibitor Interferes
with Uptake of Lipopolysaccharide by Macrophages

*
Corresponding author. Mailing address: Box 57, Weill
Medical College of Cornell University, 1300 York Ave., New York, NY
10021. Phone: (212) 746-2986. Fax: (212) 746-8536. E-mail:
ahding{at}med.cornell.edu.
Present address: Millennium Pharmaceuticals, Inc., Cambridge,
MA 02139-4815.
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