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Thrombin Differenti...
Thrombin Differentially Modulates the Acute Inflammatory Response to Escherichia coli and Staphylococcus aureus in Human Whole Blood
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- Johnson, Christina (author)
- Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway
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- Quach, Huy Quang (author)
- Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway
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- Lau, Corinna (author)
- Nordland Hosp, Norway
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- Ekholt, Karin (author)
- Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway
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- Espevik, Terje (author)
- Norwegian Univ Sci & Technol, Norway
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- Woodruff, Trent M. (author)
- Univ Queensland, Australia
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- Pischke, Soren Erik (author)
- Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway
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- Mollnes, Tom Eirik (author)
- Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway;Nordland Hosp, Norway;Norwegian Univ Sci & Technol, Norway;Univ Tromso, Norway
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- Nilsson, Per H., 1980- (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Avancerade material,Univ Oslo, Norway;RIKEN Oslo Univ Hosp, Norway,Linnaeus Ctr Biomat Chem, BMC;HoRB
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(creator_code:org_t)
- 2022-06-15
- 2022
- English.
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In: Journal of Immunology. - American Association of Immunologists : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 208:12, s. 2771-2778
- Related links:
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https://doi.org/10.4...
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Abstract
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- Thrombin plays a central role in thromboinflammatory responses, but its activity is blocked in the common ex vivo human whole blood models, making an ex vivo study of thrombin effects on thromboinflammatory responses unfeasible. In this study, we exploited the anticoagulant peptide Gly-Pro-Arg-Pro (GPRP) that blocks fibrin polymerization to study the effects of thrombin on acute inflammation in response to Escherichia coli and Staphylococcus aureus. Human blood was anticoagulated with either GPRP or the thrombin inhibitor lepirudin and incubated with either E. coli or S. aureus for up to 4 h at 37 degrees C. In GPRP-anticoagulated blood, there were spontaneous elevations in thrombin levels and platelet activation, which further increased in the presence of bacteria. Complement activation and the expression of activation markers on monocytes and granulocytes increased to the same extent in both blood models in response to bacteria. Most cytokines were not elevated in response to thrombin alone, but thrombin presence substantially and heterogeneously modulated several cytokines that increased in response to bacterial incubations. Bacterial-induced releases of IL-8, MIP-1 alpha, and mip-1 beta were potentiated in the thrombin-active GPRP model, whereas the levels of IP-10, TNF, IL-6, and IL-1 beta were elevated in the thrombin-inactive lepirudin model. Complement CS-blockade, combined with CD14 inhibition, reduced the overall cytokine release significantly, both in thrombin-active and thrombin-inactive models. Our data support that thrombin itself marginally induces leukocyte-dependent cytokine release in this isolated human whole blood but is a significant modulator of bacteria-induced inflammation by a differential effect on cytokine patterns.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Johnson, Christi ...
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Quach, Huy Quang
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Lau, Corinna
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Ekholt, Karin
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Espevik, Terje
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Woodruff, Trent ...
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Pischke, Soren E ...
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Mollnes, Tom Eir ...
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Nilsson, Per H., ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Journal of Immun ...
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Linnaeus University