The binding of CpG-oligodeoxynucleotides to cell-surface and its immunostimulatory activity are modulated by extracellular acidic pH.
Both the binding of CpG-oligodeoxynucleotides (CpG-ODNs) to cell-surface and its immunostimulatory activity were modulated by extracellular pH in present study. At neutral pH (pH 7.4), the binding of CpG-ODN to splenocyte-surface, as well as that of non-CpG-ODN, was competitively inhibited by non-specific DNA-Herring sperm DNA in a dose dependent manner, indicating their binding sites have no specificity for CpG-motif. When the extracellular pH shifted to acidic (pH 6.4), however, their binding to cell-surface markedly increased, and only the binding of non-CpG-ODN instead of CpG-ODN was inhibited by Herring sperm DNA, implying such pH change enabled CpG-ODN bind to its specific binding-site. Consistently, lymphocytes appeared more sensitive to the stimulation of CpG-ODN at acidic pH, and Herring sperm DNA inhibited the CpG-ODN-induced TNF production from splenocytes at pH 7.4, but not at pH 6.4. These results suggest the existence of membrane receptor that specifically engages CpG-ODN with high affinity only at acidic pH, and support the hypothesis that the binding CpG-ODN to its specific membrane receptor and subsequently triggering of CpG-related signaling occurred within acidified endosomes.
Hu
Zhenlin
Z
Department of Medical Genetics, The Second Military Medical University, Shanghai 200433, China.
Sun
Shuhan
S
Zhou
Fengjuan
F
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005399:Fishes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009841:Oligonucleotides / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013094:Spermatozoa / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D009841:Oligonucleotides; D010761:Phosphorus Radioisotopes; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D004247:DNA