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Antimicrobial Agents and Chemotherapy, December 1999, p. 2984-2989, Vol. 43, No. 12
Department of Infectious Diseases, Leiden
University Medical Center, Leiden, The Netherlands
Received 21 May 1998/Returned for modification 6 August
1998/Accepted 2 October 1999
Antibiotics release inflammatory fragments, such as lipoteichoic
acid (LTA) and peptidoglycan (PG), from the cell wall of Staphylococcus aureus. In this study, we exposed S. aureus cultures to a number of
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Antibiotic-Induced Cell Wall Fragments of
Staphylococcus aureus Increase Endothelial Chemokine
Secretion and Adhesiveness for Granulocytes
-lactam antibiotics (imipenem,
flucloxacillin, and cefamandole) and protein synthesis-inhibiting
antibiotics (erythromycin, clindamycin, and gentamicin) and
investigated whether supernatants of these cultures differ in their
capacity to stimulate endothelial cells (EC). After 24 h of
incubation, endothelial adhesiveness for leukocytes, surface expression
of various adhesion molecules, and secretion of the chemokines
interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were
measured. Supernatants of
-lactam-exposed cultures (designated
-lactam supernatants) enhanced the adhesiveness of EC for
granulocytes, whereas those of protein synthesis-inhibiting
antibiotic-exposed cultures (designated protein synthesis-inhibitor
supernatants) did not. This hyperadhesiveness coincided with a higher
intercellular adhesion molecule-1 expression on the surface of the
stimulated EC. In addition, EC stimulated with
-lactam supernatants
secreted significantly higher concentrations of the chemokines IL-8 and
MCP-1 than those stimulated with protein synthesis-inhibitor
supernatants. The finding that the concentrations of LTA and PG in
-lactam supernatants were much higher than those in protein
synthesis-inhibitor supernatants suggests that the observed differences
in stimulatory effect between these supernatants are a result of
differences in the release of cell wall fragments, although the
presence of other stimulatory factors in the supernatants cannot be
excluded. In conclusion, our results argue for a release of LTA and PG
from S. aureus after exposure to
-lactam antibiotics that enhances the development of a systemic inflammatory response by
stimulating EC such that adhesiveness for granulocytes is increased and
large amounts of IL-8 and MCP-1 are secreted.
*
Corresponding author. Mailing address: Department of
Infectious Diseases, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Phone: 31-71-5262613. Fax: 31-71-5266758. E-mail: jtvandissel{at}infectdis.azl.nl.
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