oru.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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
The neutrophil serine protease PR3 induces shape change of platelets via the Rho/Rho kinase and Ca2+ signaling pathways
Department of Nephrology, Qingyuan City Hospital of Jinan University, Guangdong, China; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Department of Experimental and Clinical Medicine, Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-1920-3962
Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden. Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; .
Show others and affiliations
2014 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 134, no 2, p. 418-425Article in journal (Refereed) Published
Abstract [en]

Introduction: Proteinase 3 (PR3) is released from neutrophil azurophilic granules and exerts complex effects on the inflammatory process. PR3 catalyzes the degradation of a number of macromolecules, but the consequences on blood cells are less well defined. In the present study, the effect of PR3 on human platelets was thoroughly investigated.

Methods: The experiments were performed on washed platelets freshly isolated from blood donated by healthy human volunteers. Platelets shape change and aggregation was measured on a Chrono-Log aggregometer. The phosphorylated form of MYPT1 was visualized by immunostaining. Platelet activation was further evaluated by flow cytometry.

Results: PR3 induced platelet shape change but not aggregation. Flow cytometry analysis showed that PR3 induced no P-selectin expression or binding of fibrinogen to the platelets, and it did not change the activation in response to PAR1- or PAR4-activating peptides or to thrombin. Furthermore, Fura-2 measurement and immuno-blotting analysis, respectively, revealed that PR3 stimulated small intracellular Ca2+ mobilization and Thr696-specific phosphorylation of the myosin phosphatase target subunit 1 (MYPT1). Separate treatment of platelets with the Rho/Rho kinase inhibitor Y-27632 and the intracellular Ca2+ chelator BAPTA/AM reduced the shape change induced by PR3 whereas concurrent treatment completely inhibited it.

Conclusion: The data shows that the neutrophil protease PR3 is a direct modulator of human platelets and causes shape change through activation of the Rho/Rho kinase and Ca2+ signaling pathways. This finding highlights an additional mechanism in the complex interplay between neutrophils and platelets.

Place, publisher, year, edition, pages
Oxon, United Kingdom: Elsevier, 2014. Vol. 134, no 2, p. 418-425
Keywords [en]
ANCA-associated vasculitis, Proteinase PR3, Platelet shape change, Rho/Rho kinase signaling pathway, Ca2+ signaling pathway
National Category
Hematology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-37561DOI: 10.1016/j.thromres.2014.06.001ISI: 000341309200035PubMedID: 24993595Scopus ID: 2-s2.0-84905105637OAI: oai:DiVA.org:oru-37561DiVA, id: diva2:753147
Note

Funding Agencies:

Swedish Renal Foundation

Asp Foundation

Available from: 2014-10-07 Created: 2014-10-07 Last updated: 2019-03-26Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Ramström, SofiaGrenegård, Magnus

Search in DiVA

By author/editor
Ramström, SofiaGrenegård, Magnus
By organisation
School of Medicine, Örebro University, Sweden
In the same journal
Thrombosis Research
Hematology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 357 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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