liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Synaptotagmin II could confer Ca2+ sensitivity to phagocytosis in human neutrophils
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
The Phagocyte Laboratory, Department of Medical Microbiology, Göteborg University, Göteborg, Sweden.
Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
Show others and affiliations
2002 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1590, no 1-3, 159-166 p.Article in journal (Refereed) Published
Abstract [en]

Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent processes. The calcium requirements vary between granule types, suggesting the presence of different calcium sensors. The synaptotagmins, a family of calcium-binding proteins, previously shown to participate in vesicle fusion and vesicle recycling in excitable cells, are putative calcium-sensors of exocytosis in excitable cells. In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes. In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein. Subcellular fractionation revealed that synaptotagmin II was associated with the specific granules. In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane. This correlated with the upregulation of complement receptor 3 (CR 3), reflecting the translocation of specific granules to the cell surface. Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP-1 translocated in parallel but probably was located to another subcellular compartment than synaptotagmin II. Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils.

Place, publisher, year, edition, pages
2002. Vol. 1590, no 1-3, 159-166 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26522DOI: 10.1016/S0167-4889(02)00209-4Local ID: 11081OAI: oai:DiVA.org:liu-26522DiVA: diva2:247071
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
In thesis
1. Regulation of phagocytosis and phagolysosome fusion in human leukocytes
Open this publication in new window or tab >>Regulation of phagocytosis and phagolysosome fusion in human leukocytes
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Professional phagocytes such as neutrophil granulocytes and macrophages are an esential part of the innate immune system. The neutrophils form the first line of defence against invading microorganisms and are important for rapid killing of the intruders. Macrophages arrive later at the site of infection, kill micoorganisms, degrade dead cells, present antigens and secrete substances that orchestrate the inflammatory response. Neutrophils and macrophages ingest and kill microorganisms in a process called phagocytosis, where calcium signalling has shown to be involved. Inside the cell the microorganism is enclosed in a phagosome, that sequentially fuses with various intracellular vesicles to form a phagolysosome in which the intruder is killed. Killing is achieved through the actions of lytic enzymes, nitrogen oxide (NO) and reactive oxygen metabolites (ROM). Studies on the regulation of phagocytosis are essential since many pathogens are able to survive by interfering with this process. In the first study we investigated intracellular signalling in human neutrophils following engagement of a phagocytic receptor, complement receptor 3 (CR3). For this, we used antibody-coated PANSORBINS® which bound to the ß-chain of CR3 without inducing phagocytosis. We found that these particles elicited an intracellular production of ROM which was dependent on the cytoskeleton and on phospholipase D. In the second study, we showed that the putative calcium-sensor synaptotagmin II is present in neutrophils and is involved in phagocytosis. Synaptotagmin II was found on the specific granules and translocated to the phagosome in a calcium-dependent manner during eR-mediated phagocytosis and to the plasma membrane after stimulation with the formylated peptide, N-formyl-methionyl-leucyl-phenylalanine. In the third study, we demonstrate the presence of synaptotagmin IV in human macrophages. Synaptotagmin IV translocated transiendy to macrophage phagosomes during eR- and FcγR-mediated phagocytosis. We also found that eR- and FcyR-mediated uptake was calcium dependent in these cells. In the fourth study, we show that lipophosphoglycan (LPG) from Leishmania donovani induced elevated levels of periphagosomal F-actin, inhibition of phagolysosome maturation and diminished production of ROM in neutrophils during eR-mediated phagocytosis. Together, our data show that generation of ROM occurs early during eR-mediated phagocytosis and could be involved in intracellular signalling, that synaptotagmins are present in professional phagocytes and could act as calcium sensors in phagosomal maturation and secretion, and that LPG can be used as a tool to investigate how actin can regulate phagosomal maturation in neutrophils.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 818
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26661 (URN)11227 (Local ID)91-7373-509-4 (ISBN)11227 (Archive number)11227 (OAI)
Public defence
2003-11-06, Aulan, Hälsans Hus, Universitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Lindmark, MariaSerrander, LenaRasmusson, BirgittaStendahl, Olle

Search in DiVA

By author/editor
Lindmark, MariaSerrander, LenaRasmusson, BirgittaStendahl, Olle
By organisation
Medical MicrobiologyFaculty of Health Sciences
In the same journal
Biochimica et Biophysica Acta. Molecular Cell Research
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 82 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf