Published online before print December 12, 2003

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0803360

Received for publication August 1, 2003.
Revised October 28, 2003.
Accepted for publication November 12, 2003.

Article

Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2

Sonja Lotz ^*, Eresso Aga ^*, Inga Wilde ^*, Ger van Zandbergen ^*, Thomas Hartung , Werner Solbach ^*, and Tamás Laskay ^*@

*Institute for Medical Microbiology and Hygiene, University of Lübeck, Germany; and Department of Biochemical Pharmacology, University of Konstanz, Germany

^@ To whom correspondence should be addressed. E-mail: Tamas.Laskay{at}hygiene.ukl.mu-luebeck.de.

Abstract

Lipoteichoic acid (LTA) is a major component of the cell membrane of gram-positive bacteria. Although LTA has become increasingly recognized as an immunomodulator, its effect on polymorphonuclear neutrophil granulocytes (PMN) is still not clear. The interaction between LTA and PMN, however, is of particular importance, as PMN are the first leukocytes that migrate to the site of infection and encounter bacterial pathogens. In the present study, the interaction of highly purified human PMN with endotoxin-free LTA from Staphylococcus aureus was investigated. After exposure to LTA, neutrophil granulocytes acquired typical activated cell morphology. LTA had a marked activating effect on the functions of PMN as well. Shedding of CD62L, degranulation, and priming for formyl-Met-Leu-Phe-mediated oxidative burst were induced in PMN upon exposure to LTA. Moreover, LTA treatment induced the release of proinflammatory cytokines such as interleukin-8, tumor necrosis factor , and granulocyte-colony stimulating factor by PMN. The effects of LTA on PMN were found to be associated with nuclear factor-B activation. Of particular interest was that LTA inhibited the spontaneous apoptosis and therefore, increased the lifespan of PMN. Experiments using blocking antibodies revealed that CD14 and Toll-like receptor 2 (TLR2) but not TLR4 play a major role in LTA-mediated effects on PMN. These data clearly show that LTA, a component of gram-positive bacteria, directly activates neutrophil granulocytes, the primary effector cells in the first line of defense against infectious challenge.

Key Words: PMN • LTA • gram-positive bacteria • cellular activation • inflammation

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