The host defense peptide LL-37 triggers release of nucleic acids from human mast cells
(2018) In Peptides 109. p.39-45- Abstract
The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase... (More)
The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.
(Less)
- author
- Dahl, Sara LU ; Anders, Emma LU ; Gidlöf, Olof LU ; Svensson, Daniel LU and Nilsson, Bengt Olof LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cathelicidin, Cell viability, Extracellular trap, Host defense peptide (HDP), Innate immunity, Mast cells
- in
- Peptides
- volume
- 109
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:30308233
- scopus:85054627565
- ISSN
- 0196-9781
- DOI
- 10.1016/j.peptides.2018.10.001
- language
- English
- LU publication?
- yes
- id
- 9cb02667-7ea3-45d6-96ac-2e6bca3ba609
- date added to LUP
- 2018-11-09 12:12:07
- date last changed
- 2024-08-20 03:24:18
@article{9cb02667-7ea3-45d6-96ac-2e6bca3ba609, abstract = {{<p>The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.</p>}}, author = {{Dahl, Sara and Anders, Emma and Gidlöf, Olof and Svensson, Daniel and Nilsson, Bengt Olof}}, issn = {{0196-9781}}, keywords = {{Cathelicidin; Cell viability; Extracellular trap; Host defense peptide (HDP); Innate immunity; Mast cells}}, language = {{eng}}, pages = {{39--45}}, publisher = {{Elsevier}}, series = {{Peptides}}, title = {{The host defense peptide LL-37 triggers release of nucleic acids from human mast cells}}, url = {{http://dx.doi.org/10.1016/j.peptides.2018.10.001}}, doi = {{10.1016/j.peptides.2018.10.001}}, volume = {{109}}, year = {{2018}}, }