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Platelets as immune cells in sensing bacterial infection
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university , 2015. , p. 78
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 116
Keywords [en]
Platelets, infection, TLR2/1, Porphyromonas gingivalis, inflammatory mediators, lipid peroxidation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Cell Research
Identifiers
URN: urn:nbn:se:oru:diva-40397ISBN: 978-91-7529-060-7 (print)OAI: oai:DiVA.org:oru-40397DiVA, id: diva2:777176
Public defence
2015-03-06, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-01-08 Created: 2015-01-08 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation
Open this publication in new window or tab >>Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation
2014 (English)In: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 9, no 4, p. 041003-Article in journal (Refereed) Published
Abstract [en]

Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Cell Research
Identifiers
urn:nbn:se:oru:diva-42365 (URN)10.1116/1.4901135 (DOI)000347160900004 ()25553878 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Society for Medical Research (SSMF)
Note

Funding Agencies:

Swedish Medical Research Council

Olle Engkvist Foundation

Lars Hiertas Minne foundation

Available from: 2015-02-04 Created: 2015-02-03 Last updated: 2017-12-05Bibliographically approved
2. The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation
Open this publication in new window or tab >>The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation
2015 (English)In: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, no 1, p. 62-73Article in journal (Refereed) Published
Abstract [en]

Platelets are considered to have important functions in inflammatory processes and as actors in the innate immunity. Several studies have shown associations between cardiovascular disease and periodontitis, where the oral anaerobic pathogen Porphyromonas gingivalis has a prominent role in modulating the immune response. Porphyromonas gingivalis has been found in atherosclerotic plaques, indicating spreading of the pathogen via the circulation, with an ability to interact with and activate platelets via e.g. Toll-like receptors (TLR) and protease-activated receptors. We aimed to evaluate how the cysteine proteases, gingipains, of P.gingivalis affect platelets in terms of activation and chemokine secretion, and to further investigate the mechanisms of platelet-bacteria interaction. This study shows that primary features of platelet activation, i.e. changes in intracellular free calcium and aggregation, are affected by P.gingivalis and that arg-gingipains are of great importance for the ability of the bacterium to activate platelets. The P.gingivalis induced a release of the chemokine RANTES, however, to a much lower extent compared with the TLR2/1-agonist Pam(3)CSK(4), which evoked a time-dependent release of the chemokine. Interestingly, the TLR2/1-evoked response was abolished by a following addition of viable P.gingivalis wild-types and gingipain mutants, showing that both Rgp and Kgp cleave the secreted chemokine. We also demonstrate that Pam(3)CSK(4)-stimulated platelets release migration inhibitory factor and plasminogen activator inhibitor-1, and that also these responses were antagonized by P.gingivalis. These results supports immune-modulatory activities of P.gingivalis and further clarify platelets as active players in innate immunity and in sensing bacterial infections, and as target cells in inflammatory reactions induced by P.gingivalis infection.

Keywords
gingipains, migration inhibitory factor, periodontitis, platelets, Porphyromonas gingivalis, RANTES
National Category
Microbiology in the medical area Medical and Health Sciences
Research subject
Microbiology
Identifiers
urn:nbn:se:oru:diva-42616 (URN)10.1111/omi.12067 (DOI)000347897100006 ()25043711 (PubMedID)2-s2.0-84920994869 (Scopus ID)
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agency:

Foundation of Olle Engkvist

Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2018-01-11Bibliographically approved
3. The platelet response to various strains of Porphyromonas gingivalis
Open this publication in new window or tab >>The platelet response to various strains of Porphyromonas gingivalis
(English)Manuscript (preprint) (Other academic)
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:oru:diva-43013 (URN)
Available from: 2015-02-27 Created: 2015-02-27 Last updated: 2018-01-11Bibliographically approved
4. Porphyromonas gingivalis-induced lipid peroxidation: the role of platelets, gingipains and periodontal status.
Open this publication in new window or tab >>Porphyromonas gingivalis-induced lipid peroxidation: the role of platelets, gingipains and periodontal status.
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-43014 (URN)
Available from: 2015-02-27 Created: 2015-02-27 Last updated: 2018-01-11Bibliographically approved

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Klarström-Engström, Kristin

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