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Immunostimulatory DNA induces degranulation and NADPH-oxidase activation in human neutrophils while concomitantly inhibiting chemotaxis and phagocytosis

Journal article
Authors Johan Bylund
Marie Samuelsson
Andrej Tarkowski
Anna Karlsson
Vincent Collins
Published in Eur J Immunol
Volume 32
Issue 10
Pages 2847-56
Publication year 2002
Published at Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
Pages 2847-56
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adjuvants, Immunologic/*pharmacology, Cell Degranulation/*drug effects, Chemotaxis, Leukocyte/*drug effects, Enzyme Activation, Humans, N-Formylmethionine Leucyl-Phenylalanine/pharmacology, NADPH Oxidase/*metabolism, Neutrophils/*drug effects/enzymology/physiology, Oligodeoxyribonucleotides/*pharmacology, Phagocytosis/*drug effects, Thionucleotides/*pharmacology
Subject categories Medical and Health Sciences

Abstract

We examined the effects of oligodeoxynucleotides (ODN) with different structures and sequences on human neutrophil function. In lymphocytes and monocytes, the CpG-mediated immunostimulation is dependent on motif content, flanking sequences and DNA backbone composition. In neutrophils, however, native phosphodiester ODN were without effect regardless of CpG content, while backbone-substituted phosphorothioate ODN (PS-ODN) modulated neutrophil function in a sequence-independent manner. The neutrophil respiratory burst and degranulation of the specific and gelatinase granules were markedly increased by PS-ODN, as was the shedding of L-selectin. In contrast, neutrophil chemotaxis and phagocytosis were inhibited by PS-ODN. In summary, PS-ODN have both stimulatory and inhibitory effects on neutrophil function. This impact of PS-ODN on neutrophil function is unique and distinct from that exerted on other immune cells, with respect to both the identity of the activating DNA molecules and the regulation of the effector functions. These findings may have implications for the development of DNA-based immunotherapy and vaccination.

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