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Bacterial DNA promotes neutrophil adhesion to endothelial cells
Author(s) -
Jozsef Levente,
Kebir Driss El,
Khreiss Tarek,
Filep Janos G
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a125-c
Subject(s) - cpg site , dna , microbiology and biotechnology , dna methylation , cell adhesion , adhesion , umbilical vein , chemistry , biology , gene , gene expression , biochemistry , in vitro , organic chemistry
Bacterial DNA can be detected in the absence of bacteria in chronic inflammatory conditions. Bacterial DNA is emerging as an important regulator of functions of human neutrophil granulocytes. Bacterial DNA contains short sequences of nonmethylated CpG dinucleotides (CpG‐DNA) that are recognized by TLR‐9. We investigated the impact of CpG‐DNA on neutrophil adherence to human umbilical vein endothelial cells (HUVEC). HUVEC express TLR‐9 and respond to CpG‐DNA (0.2–20 μg/ml), but not to thymus DNA, with increased expression of E‐selectin and ICAM‐1 protein and mRNA. Methylation of cytosines in CpG‐DNA resulted in a complete loss of activity. Neutrophil adhesion to HUVEC activated with CpG‐DNA was markedly enhanced under low shear conditions. The number of adherent neutrophils was further enhanced when the adhesion assay was performed in the presence of CpG‐DNA, indicating that CpG‐DNA activates both neutrophils and HUVEC. The adhesive interactions were blocked by antibodies against CD18 (~70% inhibition), E‐selectin and L‐selectin. Combination of the three antibodies inhibited adhesion by 87%. These results identify HUVEC as a target for bacterial DNA and indicate that by enhancing neutrophil adhesion to endothelial cells bacterial DNA may contribute to maintenance and aggravation of the inflammatory response. (Supported by CIHR grant MOP‐67054).