| 1. |
- Herwald, Heiko, et al.
(författare)
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Foreword
- 2011
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Ingår i: Sepsis - Pro-Inflammatory and Anti-Inflammatory Responses : Good, Bad or Ugly? - Good, Bad or Ugly?. - Basel : KARGER. - 1662-291X .- 1420-9519. - 9783805597104 - 9783805597111 ; 17
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Papareddy, Praveen, et al.
(författare)
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A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
- 2019
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2442-2455
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Tidskriftsartikel (refereegranskat)abstract
- Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-kappa B. We found that the modulating effect is primarily restricted to the less abundant beta-isoform (h beta AT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of h beta AT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or h beta AT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with h beta AT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
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| 3. |
- Ali, Mohamad N., et al.
(författare)
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TFPI-2 protects against gram-negative bacterial infection
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:SEP
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Tidskriftsartikel (refereegranskat)abstract
- Tissue factor pathway inhibitor-2 (TFPI-2) has previously been characterized as an endogenous anticoagulant. TFPI-2 is expressed in the vast majority of cells, mainly secreted into the extracellular matrix. Recently we reported that EDC34, a C-terminal peptide derived from TFPI-2, exerts a broad antimicrobial activity. In the present study, we describe a previously unknown antimicrobial mode of action for the human TFPI-2 C-terminal peptide EDC34, mediated via binding to immunoglobulins of the classes IgG, IgA, IgE, and IgM. In particular the interaction of EDC34 with the Fc part of IgG is of importance since this boosts interaction between the immunoglobulin and complement factor C1q. Moreover, we find that the binding increases the C1q engagement of the antigen-antibody interaction, leading to enhanced activation of the classical complement pathway during bacterial infection. In experimental murine models of infection and endotoxin challenge, we show that TFPI-2 is up-regulated in several organs, including the lung. Correspondingly, TFPI-2-/- mice are more susceptible to pulmonary Pseudomonas aeruginosa bacterial infection. No anti-coagulant role of TFPI-2 was observed in these models in vivo. Furthermore, in vivo, the mouse TFPI-2-derived C-terminal peptide VKG24, a homolog to human EDC34 is protective against systemic Escherichia coli bacterial infection. Moreover, in sputum from cystic fibrosis patients TFPI-2 C-terminal fragments are generated and found associated with immunoglobulins. Together our data describe a previously unknown host defense mechanism and therapeutic importance of TFPI-2 against invading Gram-negative bacterial pathogens.
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| 4. |
- Bhongir, Ravi K. V., et al.
(författare)
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DNA-fragmentation is a source of bactericidal activity against Pseudomonas aeruginosa
- 2017
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Ingår i: Biochemical Journal. - 0264-6021. ; 474:3, s. 411-425
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Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa airway infection is common in cystic fibrosis (CF), a disease also characterized by abundant extracellular DNA (eDNA) in the airways. The eDNA is mainly derived from neutrophils accumulating in the airways and contributes to a high sputum viscosity. The altered environment in the lower airways also paves the way for chronic P. aeruginosa infection. Here, we show that mice with P. aeruginosa airway infection have increased survival and decreased bacterial load after topical treatment with DNase. Furthermore, DNA from the sputum of CF patients showed increased bactericidal activity after treatment with DNase ex vivo. Both degraded DNA of neutrophil extracellular traps (NETs) and genomic DNA degraded by serum, acquired bactericidal activity against P. aeruginosa. In vitro, small synthetic DNA-fragments (<100 base pairs) but not large fragments nor genomic DNA, were bactericidal against Gram-negative but not Grampositive bacteria. The addition of divalent cations reduced bacterial killing, suggesting that chelation of divalent cations by DNA results in destabilization of the lipopolysaccharide (LPS) envelope. This is a novel antibacterial strategy where fragmentation of eDNA and DNA-fragments can be used to treat P. aeruginosa airway infection.
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| 5. |
- Egesten, Arne, et al.
(författare)
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A Leak in the Dike
- 2020
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 12:5, s. 355-356
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Egesten, Arne, et al.
(författare)
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Catch me if you can or actors on the run
- 2018
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 11:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Egesten, Arne, et al.
(författare)
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Going Fishing
- 2018
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Egesten, Arne, et al.
(författare)
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Journal of Innate Immunity Ten Years Later
- 2018
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:5-6, s. 363-364
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Egesten, Arne, et al.
(författare)
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Mast Cells and More
- 2021
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:3, s. 129-130
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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