Bacterial DNA delays human eosinophil apoptosis

Abstract

To cite this version:Pinja Ilmarinen, Hannele Hasala, Outi Sareila, Eeva Moilanen, Hannu Kankaanranta. Bacterial DNA delays human eosinophil apoptosis. Pulmonary Pharmacology & Therapeutics, 2009, 22 (3), pp.167. <10.1016/j.pupt.2008.11.012>. <hal-00530439>Please cite this article as: Ilmarinen P, Hasala H, Sareila O, Moilanen E, Kankaanranta H. Bacterial DNA delays human eosinophil apoptosis, Pulmonary Pharmacology & Therapeutics (2008), doi: 10.1016/j.pupt.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ODNs had occasionally parallel but less profound effect on eosinophil apoptosis, which was not dependent on endosomal acidification. The anti-apoptotic effect of CpG AcceptedODNs was dependent on phosphatidylinositol 3-kinase (PI3K) and nuclear factor-κB (NF-κB) but not mitogen-activated protein kinases (MAPKs) as determined by inhibitor studies. Although our results suggest CpG-dependent involvement of TLR9 in the action of phosphorothioate-modified ODNs, we interestingly found that the antiapoptotic action of native bacterial DNA in eosinophils is not dependent on unmethylated CpG motifs. This suggests that bacterial DNA contains a currently unknown recognition structure lacking from vertebrate DNA. Bacterial DNA-mediated suppression of eosinophil apoptosis is a novel mechanism for exacerbation of eosinophilic lung inflammation associated with bacterial respiratory tract infection.

Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism

“…The cells showing decreased relative DNA content were considered to be apoptotic. The results were confirmed by showing the changes in phosphatidylserine (PS) expression on the surface of eosinophils by using the Annexin-V binding assay as previously reported [19,21]. The cells displaying positive Annexin-V FITC labelling (FITC+/PI-and FITC+/PI+) were regarded as apoptotic [21].…”

“…14 characterised effects of TNF-α, interferon α/γ or TLR9 activation [21,31,32]. One may argue that the effect of salbutamol is small and thus clinically irrelevant.…”

The Fluorescein-derived Dye Aminophenyl Fluorescein Is a Suitable Tool to Detect Hypobromous Acid (HOBr)-producing Activity in Eosinophils

“…Eosinophils were isolated from the blood using the same protocol followed by a negative immunomagnetic selection of eosinophils (4). Briefly, CD16 antibodies linked to magnetic beads were used to retain neutrophils on a column with a ferromagnetic matrix (2,32). Purity of the cells was tested by staining with CD16-FITC and CCR3-allophycocyanin antibodies and flow cytometry.…”

“…However, dysregulations regarding these cells have physiological relevance. The delayed apoptosis of eosinophils is a key feature of the pathogenesis of asthma (2)(3)(4). Other airway diseases such as chronic obstructive pulmonary disease as well as allergic diseases like allergic rhinitis are also accompanied by an impaired eosinophil apoptosis (5)(6)(7).…”

“…Other airway diseases such as chronic obstructive pulmonary disease as well as allergic diseases like allergic rhinitis are also accompanied by an impaired eosinophil apoptosis (5)(6)(7). Granule proteins, proinflammatory mediators, and reactive oxygen species from these cells are regarded as important mediators for chronic proinflammatory and autoimmune conditions (2,3,5).…”