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Bacterial DNA activates neutrophils through a CpG- and TLR9-independent mechanism. Neutrophil activation does not require DNA internalization, suggesting that it results from the interaction of bacterial DNA with a neutrophil surface receptor. The aim of this study was to characterize the interaction of bacterial DNA with the neutrophil surface. Bacterial DNA binding showed saturation and was inhibited by unlabeled DNA but not by other polyanions like yeast tRNA and poly-A. Resembling the conditions under which bacterial DNA triggers neutrophil activation, binding was not modified in the presence or absence of calcium, magnesium or serum. Treatment of neutrophils with proteases not only dramatically reduced bacterial DNA binding but also inhibited neutrophil activation induced by bacterial DNA. Experiments performed with DNA samples of different lengths obtained after digestion of bacterial DNA with DNase showed that only DNA fragments greater than ≈170-180 nucleotides competed bacterial DNA binding and retained the ability to trigger cell activation. Treatment of neutrophils with chemoattractants or conventional agonists significantly increased bacterial DNA binding. Moreover, neutrophils that underwent transmigration through human endothelial cell monolayers even in the absence of chemoattractants, exhibited higher binding levels of bacterial DNA. Together, our findings provide evidence that binding of bacterial DNA to neutrophils is a receptor-mediated process that conditions the ability of DNA to trigger cell activation. We speculate that neutrophil recognition of bacterial DNA might be modulated by the balance of agonists present at inflammatory foci. This effect might be relevant in bacterial infections with a biofilm etiology, in which extracellular DNA could function as a potent neutrophil agonist. © 2008 USCAP, Inc All rights reserved.


Documento: Artículo
Título:Characterization of bacterial DNA binding to human neutrophil surface
Autor:Fuxman Bass, J.I.; Gabelloni, M.L.; Alvarez, M.E.; Vermeulen, M.E.; Russo, D.M.; Zorreguieta, Á.; Geffner, J.R.; Trevani, A.S.
Filiación:Departamento de Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina
Departamento de Fisiología Y Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Fundación Instituto Leloir, IIB-BA CONICET, Buenos Aires, Argentina
Department of Immunology, IIHEMA-Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina
Palabras clave:Bacterial DNA binding; Biofilm; CpG; Inflammation; Neutrophils; TLR9; bacterial DNA; chemoattractant; deoxyribonuclease; article; biotinylation; cell culture; cell isolation; cell migration; cell surface; controlled study; DNA binding; human; human cell; neutrophil; priority journal; Base Sequence; Biofilms; Cells, Cultured; DNA Primers; DNA, Bacterial; Escherichia coli; Humans; Neutrophils
Página de inicio:926
Página de fin:937
Título revista:Laboratory Investigation
Título revista abreviado:Lab. Invest.
CAS:deoxyribonuclease, 37211-67-9; DNA Primers; DNA, Bacterial


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---------- APA ----------
Fuxman Bass, J.I., Gabelloni, M.L., Alvarez, M.E., Vermeulen, M.E., Russo, D.M., Zorreguieta, Á., Geffner, J.R.,..., Trevani, A.S. (2008) . Characterization of bacterial DNA binding to human neutrophil surface. Laboratory Investigation, 88(9), 926-937.
---------- CHICAGO ----------
Fuxman Bass, J.I., Gabelloni, M.L., Alvarez, M.E., Vermeulen, M.E., Russo, D.M., Zorreguieta, Á., et al. "Characterization of bacterial DNA binding to human neutrophil surface" . Laboratory Investigation 88, no. 9 (2008) : 926-937.
---------- MLA ----------
Fuxman Bass, J.I., Gabelloni, M.L., Alvarez, M.E., Vermeulen, M.E., Russo, D.M., Zorreguieta, Á., et al. "Characterization of bacterial DNA binding to human neutrophil surface" . Laboratory Investigation, vol. 88, no. 9, 2008, pp. 926-937.
---------- VANCOUVER ----------
Fuxman Bass, J.I., Gabelloni, M.L., Alvarez, M.E., Vermeulen, M.E., Russo, D.M., Zorreguieta, Á., et al. Characterization of bacterial DNA binding to human neutrophil surface. Lab. Invest. 2008;88(9):926-937.