TY - JOUR
T1 - Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2
AU - Lotz, Sonja
AU - Aga, Eresso
AU - Wilde, Inga
AU - Van Zandbergen, Ger
AU - Hartung, Thomas
AU - Solbach, Werner
AU - Laskay, Tamás
PY - 2004/3
Y1 - 2004/3
N2 - 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 hmnan 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 α, and granulocyte-colony stimulating factor by PMN. The effects of LTA on PMN were found to be associated with nuclear factor-κB 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 infections challenge.
AB - 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 hmnan 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 α, and granulocyte-colony stimulating factor by PMN. The effects of LTA on PMN were found to be associated with nuclear factor-κB 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 infections challenge.
KW - Cellular activation
KW - Gram-positive bacteria
KW - Inflammation
KW - LTA
KW - PMN
UR - http://www.scopus.com/inward/record.url?scp=1542283732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542283732&partnerID=8YFLogxK
U2 - 10.1189/jlb.0803360
DO - 10.1189/jlb.0803360
M3 - Article
C2 - 14673018
AN - SCOPUS:1542283732
SN - 0741-5400
VL - 75
SP - 467
EP - 477
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -