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
Enhancement of chemoattractant-induced oxidative activation during phagocytosis of Staphylococcus aureus by human neutrophils
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Several studies have shown that the production of oxygen radicals in human neutrophils can be influenced by prior exposure to different priming agents, but the mechanism underlying priming is not fully understood. The present study shows that under reduced Ca2+-conditions, phagocytosis of viable, but not heat-killed S. aureus can prepare Ca2+-depleted neutrophils for an increased oxidative activation when stimulated with fMLP in the presence of Ca2+. This enhancement of the produced oxygen radicals, induced by viable S. aureus, was not due to differences in phagocytic uptake between viable or heat-killed bacteria by the neutrophils. We could neither detect any difference in the upregulation of chemoattractant receptors such as the fMLP receptor or complement receptor 3 (CR3) to the neutrophil cell surface. Phagocytosis of viable S. aureus by Ca2+-depleted neutrophils under reduced Ca2+-conditions, induced tyrosine phosphorylation of two proteins identified as phospholipase Cγ2 (PLCγ2) and Syk. Pretreatment of neutrophils with U-73122 or piceatannol, to selectively inhibit PLC and Syk, respectively, resulted in a marked suppression of the oxidative response in primed neutrophils. In addition, PP1, a drug known to selectively inhibit Srcfamily protein kinases inhibited the oxidative response in primedneutrophils. Moreover, bacterial uptake activated the Src- family protein kinase Lyn, which was inhibited by PPl. Phagocytosis of viable or heatkilled S. aureus did not show any difference in activation of p38 mitogenactivated protein kinase (MAPK) and inhibition of this kinase by SB203580 did not suppress the fMLP-induced oxidative activation inprimed neutrophils. The findings demonstrate that both priming and the induction of tyrosine phosphorylation of PLCγ2, Syk and Lyn are Ca2+-independent events, thus indicating that the phosphorylation of these intracellular targets plays a central role during the neutrophil priming by S. aureus.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79589OAI: oai:DiVA.org:liu-79589DiVA: diva2:543864
Available from: 2012-08-10 Created: 2012-08-10 Last updated: 2012-08-10Bibliographically approved
In thesis
1. On the interaction between human neutrophils and Staphylococcus aureus
Open this publication in new window or tab >>On the interaction between human neutrophils and Staphylococcus aureus
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Intracellular free calcium is a key second messenger and has been shown to regulate several crucial functions in human neutrophils. The results show that a rise in [Ca2+], is an absolute requirement for efficient killing of serum-opsonized Staphylococcus aureus by human neutrophils. The reduced killing in the absence of Ca2+ was not due to an inhibited ingestion of the S. aureus bacteria but to impairment of the subsequent production of oxygen radicals.

S. aureus is a bacterium which binds to extracellular matrix proteins such as vitronectin. When studying the role of Ca2+ during phagocytosis of S. aureus adherent to vitronectin-coated surfaces, the results show that a rise in [Ca2+], is not a prerequisite for ingestion per se. However, Ca2+ control neutrophil migration on vitronectin, by regulating reversible integrindependent adhesion of the neutrophils.

The intracellular signalling events of the neutrophils induced by S. aureus were also evaluated. The results demonstrate that S. aureus induces both priming and apoptosis in the neutrophils. This was restricted to viable and not heat-killed bacteria. During priming tyrosine phosphorylation of PLCγ2 and Syk is increased. In addition, the Src-family protein kinase Lyn is activated as well by these bacteria. Inhibition of these proteins by selective drugs abrogates priming of the neutrophils, indicating that these proteins participate in neutrophil priming. Interaction of neutrophils with S. aureus as well as a S. aureus-derived factor induces apoptosis in the neutrophils, and this is regulated by p38 MAPK.

Taken together, this investigation shows that the Ca2+-dependent processing of bacteria by human neutrophils leads to several cellular responses affecting inflammation, such as oxidative activation, tyrosine phosphorylation, priming and apoptosis.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 60 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 634
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28652 (URN)13808 (Local ID)91-7219-735-8 (ISBN)13808 (Archive number)13808 (OAI)
Public defence
2000-05-30, Elsa Brändströmssalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-08-10Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Wilsson, ÅsaStendahl, OlleMajeed, Meytham

Search in DiVA

By author/editor
Wilsson, ÅsaStendahl, OlleMajeed, Meytham
By organisation
Medical MicrobiologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 25 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