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Platelet-derived mi...
Platelet-derived microparticles regulates thrombin generation via phophatidylserine in abdominal sepsis
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- Wang, Yongzhi (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Zhang, Su (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Luo, Lingtao (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Norström, Eva (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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- Braun, Oscar Ö (författare)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Heart Failure and Mechanical Support,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Mörgelin, Matthias (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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(creator_code:org_t)
- 2017-06-06
- 2018
- Engelska 10 s.
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 1097-4652 .- 0021-9541. ; 233:2, s. 1051-1060
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Sepsis is associated with dysfunctional coagulation. Recent data suggest that platelets play a role in sepsis by promoting neutrophil accumulation. Herein, we show that cecal ligation and puncture (CLP) triggered systemic inflammation, which is characterized by formation of IL-6 and CXC chemokines as well as neutrophil accumulation in the lung. Platelet depletion decreased neutrophil accumulation, IL-6, and CXC chemokines formation in septic lungs. Depletion of platelets increased peak thrombin formation and total thrombin generation (TG) in plasma from septic animals. CLP elevated circulating levels of platelet-derived microparticles (PMPs). In vitro generated PMPs were a potent inducer of TG. Interestingly, in vitro wild-type recombinant annexin V abolished PMP-induced thrombin formation whereas a mutant annexin V protein, which does not bind to phosphatidylserine (PS), had no effect. Administration of wild-type, but not mutant annexin V, significantly inhibited thrombin formation in septic animals. Moreover, CLP-induced formation of thrombin-antithrombin complexes were reduced in platelet-depleted mice and in animals pretreated with annexin V. PMP-induced TG attenuated in FXII- and FVII-deficient plasma. These findings suggest that sepsis-induced TG is dependent on platelets. Moreover, PMPs formed in sepsis are a potent inducer of TG via PS exposure, and activation of both the intrinsic and extrinsic pathway of coagulation. In conclusion, these observations suggest that PMPs and PS play an important role in dysfunctional coagulation in abdominal sepsis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Animals
- Annexin A5/blood
- Antithrombin III
- Blood Coagulation
- Blood Platelets/immunology
- Cell-Derived Microparticles/immunology
- Chemokines, CXC/metabolism
- Disease Models, Animal
- Inflammation/blood
- Interleukin-6/metabolism
- Lung/immunology
- Male
- Mice, Inbred C57BL
- Neutrophil Infiltration
- Peptide Hydrolases/blood
- Phosphatidylserines/blood
- Sepsis/blood
- Signal Transduction
- Thrombin/metabolism
- Time Factors
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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