| 1. |
- Herwald, Heiko, et al.
(författare)
-
Foreword
- 2011
-
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
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 2. |
- Papareddy, Praveen, et al.
(författare)
-
A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
- 2019
-
Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2442-2455
-
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.
|
|
| 3. |
- Agar, Cetin, et al.
(författare)
-
beta(2)-Glycoprotein I: a novel component of innate immunity
- 2011
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:25, s. 6939-6947
-
Tidskriftsartikel (refereegranskat)abstract
- Sepsis is a systemic host response to invasive infection by bacteria. Despite treatment with antibiotics, current mortality rates are in the range of 20%-25%, which makes sepsis the most important cause of death in intensive care. Gram-negative bacteria are a prominent cause of sepsis. Lipopolysaccharide (LPS), one of the major constituents of the outer membrane of Gram-negative bacteria, plays a major role in activating the host's immune response by binding to monocytes and other cells. Several proteins are involved in neutralization and clearance of LPS from the bloodstream. Here, we provide evidence that beta(2)-glycoprotein I (beta(2)GPI) is a scavenger of LPS. In vitro, beta(2)GPI inhibited LPS-induced expression of tissue factor and IL-6 from monocytes and endothelial cells. Binding of beta(2)GPI to LPS caused a conformational change in beta(2)GPI that led to binding of the beta(2)GPI-LPS complex to monocytes and ultimately clearance of this complex. Furthermore, plasma levels of beta(2)GPI were inversely correlated with temperature rise and the response of inflammatory markers after a bolus injection of LPS in healthy individuals. Together, these observations provide evidence that beta(2)GPI is involved in the neutralization and clearance of LPS and identify beta(2)GPI as a component of innate immunity. (Blood. 2011;117(25):6939-6947)
|
|
| 4. |
- Ali, Mohamad N., et al.
(författare)
-
TFPI-2 protects against gram-negative bacterial infection
- 2018
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:SEP
-
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.
|
|
| 5. |
- Anders, Emma, et al.
(författare)
-
Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1 : a novel mechanism for regulation of MCP-1 production and function
- 2018
-
Ingår i: Biochemical Journal. - 0264-6021. ; 475:4, s. 775-786
-
Tidskriftsartikel (refereegranskat)abstract
- The protein gC1qR (globular C1q receptor), also named p33, was originally identified as a binding partner of the globular heads of C1q in the complement system. gC1qR/p33 is abundantly expressed in many cell types, but the functional importance of this protein is not completely understood. Here, we investigate the impact of gC1qR/p33 on the production and function of the pathophysiologically important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production of MCP-1, but had no effect on the expression of transcript for MCP-1 in human periodontal ligament cells, suggesting a translational/post-translational mechanism of action. Laser scanning confocal microscopy showed considerable cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface plasmon resonance analysis revealed a high-affinity binding (KD = 10.9 nM) between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes, pointing to a functional importance of the interaction between gC1qR/p33 and MCP-1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that gC1qR/ p33 stabilizes MCP-1, hence preventing its degradation. We propose that endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the MCP-1 protein and stimulation of its activity in human periodontal ligament cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of action.
|
|
| 6. |
- Ben Nasr, Abdelhakim, et al.
(författare)
-
Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin
- 1997
-
Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 326:3, s. 657-660
-
Tidskriftsartikel (refereegranskat)abstract
- H-kininogen (high-molecular-mass kininogen, HK) is the precursor of the vasoactive peptide hormone bradykinin (BK). Previous work has demonstrated that HK binds to Streptococcus pyogenes through M-proteins, fibrous surface proteins and important virulence factors of these bacteria. Here we find that M-protein-expressing bacteria absorb HK from human plasma. The HK bound to the bacteria was found to be cleaved, and analysis of the degradation pattern suggested that the cleavage of HK at the bacterial surface is associated with the release of BK. Moreover, addition of activated plasma prekallikrein to bacteria preincubated with human plasma, resulted in BK release. This mechanism, by which a potent vasoactive and proinflammatory peptide is generated at the site of infection, should influence the host-parasite relationship during S. pyogenes infections.
|
|
| 7. |
- Ben Nasr, Abdelhakim, et al.
(författare)
-
Human kininogens interact with M protein, a bacterial surface protein and virulence determinant.
- 1995
-
Ingår i: Biochemical Journal. - 0264-6021. ; 305:1, s. 80-173
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes, the most significant streptococcal species in clinical medicine, expresses surface proteins with affinity for several human plasma proteins. Here we report that kininogens, the precursors to the vasoactive kinins, bind to the surface of S. pyogenes. M protein, a surface molecule and a major virulence factor-in these bacteria, occurs in > 80 different serotypes. Among 49 strains of S. pyogenes, all of different M serotypes, 41 bound radiolabelled kininogens, whereas 6 M protein-negative mutant strains showed no affinity. M protein of most serotypes bind fibrinogen, and among the 55 strains tested, binding of kininogens was closely correlated to fibrinogen binding (r = 0.88, P < 0.0001). Western blotting, slot binding and enzyme immunoassay experiments demonstrated that M proteins isolated from S. pyogenes of three different M protein serotypes (M1, M6 and M46) bound kininogens. The affinity between kininogens and M1 protein was determined to be 5 x 10(7) M-1 and < or = 10(6) M-1 for high molecular weight (H-kininogen) and low molecular weight kininogen, respectively. The kininogen binding site was tentatively mapped to the N-terminal portion of M1 protein, and this site does not overlap the specific and separate binding sites for albumin, IgG and fibrinogen using monoclonal antibodies to, and synthetic peptides of, the kininogen sequence, the major M protein-binding site(s) was mapped to the C-terminal portion of the H-kininogen light chain. We anticipate that the kininogen-M protein interaction contributes to the host-parasite relationship in S. pyogenes infections.
|
|
| 8. |
- Bengtson, Sara, et al.
(författare)
-
Activation of TAFI on the Surface of Streptococcus pyogenes Evokes Inflammatory Reactions by Modulating the Kallikrein/Kinin System
- 2009
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 1:1, s. 18-28
-
Tidskriftsartikel (refereegranskat)abstract
- Bacteria-controlled regulation of host responses to infection is an important virulence mechanism that has been demonstrated to contribute to disease progression. Here we report that the human pathogen Streptococcus pyogenes employs the procarboxypeptidase TAR (thrombin-activatablefibrinolysis inhibitor) to modulate the kallikrein/kinin system. To this end, bacteria initiate a chain of events starting with the recruitment and activation of TAFI. This is followed by the assembly and induction of the contact system at the streptococcal surface, eventually triggering the release of bradykinin (BK). BK is then carboxyterminally truncated by activated TAFI, which converts the peptide from a kinin B-2 receptor ligand to a kinin B-1 receptor (B1R) agonist. Finally, we show that streptococcal supernatants indirectly amplify the B1R response as they act on peripheral blood mononuclear cells to secrete inflammatory cytokines that in turn stimulate upregulation of the B1R on human fibroblasts. Taken together our findings implicate a critical and novel role for streptococci-bound TAR, as it processes BK to a B1R agonist at the bacterial surface and thereby may redirect inflammation from a transient to a chronic state. Copyright (C) 2008 S. Karger AG, Basel
|
|
| 9. |
- Bengtson, Sara H, et al.
(författare)
-
Kinin receptor expression during Staphylococcus aureus infection.
- 2006
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:6, s. 2055-2063
-
Tidskriftsartikel (refereegranskat)abstract
- An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community- and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteria-triggered contact activation, and conversion of bradykinin to its metabolite desArg9bradykinin. The data of the present study implicate an important and previously unknown role for kinin receptor regulation in S aureus infections.
|
|
| 10. |
- Bengtson, Sara, et al.
(författare)
-
Regulation of kinin B(2) receptors by bradykinin in human lung cells.
- 2008
-
Ingår i: Biological Chemistry. - 1437-4315. ; 389, s. 1435-1440
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Bradykinin is a potent mediator of inflammation that has been shown to participate in allergic airway inflammation. The biologic effects of bradykinin are mediated by binding and activating its cognate receptor, the B(2) receptor (B(2)R). In the lung fibroblast cell line IMR-90, binding of bradykinin to the B(2)R triggers down-regulation of the receptor surface expression, suggesting that bradykinin-induced inflammation is transient and self-limited. Notably, subjects with chronic airway inflammation continue to respond to BK following a first challenge. B(2)Rs are expressed on many different lung cell types, including airway epithelial cells. We therefore compared IMR-90 cells with the human lung epithelial cell line BEAS2B and found that B2R expression in the two cell types is differently regulated by BK. While BK induces a down-regulation of B(2)R in IMR-90 cells, the same treatment leads to an up-regulation of the receptor in BEAS2B cells. These results provide a possible explanation for the potency of bradykinin in inducing ongoing airway inflammation.
|
|
| 11. |
- Beran, Ondrej, et al.
(författare)
-
Heparin-binding protein as a biomarker of circulatory failure during severe infections: A report of three cases
- 2010
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42:8, s. 634-636
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report 3 cases of disease - leptospirosis, tropical malaria and fulminant meningococcaemia - associated with high serum concentrations of heparin-binding protein (HBP) and haemodynamic instability. Furthermore, HBP kinetics were observed for the first 3 days in survivors and were correlated with improvement in clinical condition.
|
|
| 12. |
- Berkestedt, Ingrid, et al.
(författare)
-
Early depletion of contact system in patients with sepsis : a prospective matched control observational study
- 2018
-
Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; , s. 892-898
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of the contact system generates bradykinin from high-molecular-weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high-molecular-weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis-3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90-day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to controls (130 [86–255] pg/ml, p < 0.025) and did not correlate with mortality or severity of circulatory derangement. High-molecular-weight kininogen levels were lower in sepsis patients (1.6 [0.8–4.8] densitometry units) compared to controls (4.4 [2.9–7.7] densitometry units, p < 0.001), suggesting previous contact system activation. High-molecular-weight kininogen levels were lower in non-survivors than survivors (p = 0.003) and negatively correlated to severity of circulatory derangement. We conclude that a role for bradykinin in later stages of severe sepsis must be challenged. Low high-molecular-weight kininogen concentrations suggest that the decrease in bradykinin is due to substrate depletion.
|
|
| 13. |
- Berkestedt, Ingrid, et al.
(författare)
-
Elevated Plasma Levels of Antimicrobial Polypeptides in Patients with Severe Sepsis.
- 2010
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:5, s. 478-482
-
Tidskriftsartikel (refereegranskat)abstract
- We wanted to investigate if plasma levels of antimicrobial polypeptides (AMPs) are increased in severe sepsis and if they correlate with severity and mortality. Samples were collected from 31 sepsis patients at the intensive care unit. The Sequential Organ Failure Assessment (SOFA) score and 90-day mortality were registered, and inflammatory markers and AMP levels were measured by ELISA. A median SOFA score (13) and cardiovascular SOFA score (3) indicated multiorgan failure with severe circulatory derangement, and elevated cytokine levels indicated inflammatory activation. Levels of bactericidal/permeability-increasing protein, heparin-binding protein, alpha-defensins and lactoferrin but not LL-37 were elevated in sepsis patients compared with controls. Bactericidal/permeability-increasing protein levels correlated with mortality, with lower levels in survivors. Levels of all AMPs, except LL-37, positively correlated with the cardiovascular SOFA score. In conclusion, levels of several AMPs are increased in sepsis and correlate with circulatory derangement. This probably reflects neutrophil activation as part of an innate immune response.
|
|
| 14. |
- Bhongir, Ravi K. V., et al.
(författare)
-
DNA-fragmentation is a source of bactericidal activity against Pseudomonas aeruginosa
- 2017
-
Ingår i: Biochemical Journal. - 0264-6021. ; 474:3, s. 411-425
-
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.
|
|
| 15. |
- Blanchet, Xavier, et al.
(författare)
-
Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome
- 2014
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 112:6, s. 1277-1287
-
Tidskriftsartikel (refereegranskat)abstract
- Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.
|
|
| 16. |
- Chalupa, P., et al.
(författare)
-
Evaluation of potential biomarkers for the discrimination of bacterial and viral infections
- 2011
-
Ingår i: Infection. - : Springer Science and Business Media LLC. - 1439-0973 .- 0300-8126. ; 39:5, s. 411-417
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Timely knowledge of the bacterial etiology and localization of infection are important for empirical antibiotic therapy. Thus, the goal of this study was to evaluate routinely used biomarkers together with novel laboratory parameters in the diagnosis of infection. Methods In this prospective study, 54 adult patients with bacterial infections admitted to the Department of Infectious Diseases were included. For comparison, 27 patients with viral infections were enrolled. In these patients, white blood cell (WBC) counts, differential blood counts, serum levels of procalcitonin (PCT), IL-1 beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, IFN-gamma, soluble CD14 (sCD14), heparin-binding protein (HBP), cortisol (Cort), and monocyte surface expression of TLR2, TLR4, HLA-DR, and CD14 were analyzed. Also, these biomarkers were evaluated in 21 patients with acute community-acquired bacterial pneumonia (CABP), as well as in 21 patients with pyelonephritis and urosepsis. Results The highest sensitivity and specificity (expressed as the area under the curve [AUC]) for bacterial infection were observed in serum concentration of PCT (0.952), neutrophil and lymphocyte counts (0.852 and 0.841, respectively), and serumlevels of HBP (0.837), IL-6 (0.830), and Cort (0.817). In addition, the serum levels of IFN-gamma and Cort were significantly higher and IL-8 levels were lower in CABP when compared to pyelonephritis or urosepsis. Conclusions From the novel potential biomarkers, only PCT demonstrated superiority over the routine parameters in the differentiation of bacterial from viral infections. However, some of the novel parameters should be further evaluated in larger and better characterized cohorts of patients in order to find their clinical applications.
|
|
| 17. |
- Chew, Michelle, et al.
(författare)
-
Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study.
- 2012
-
Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 61:4, s. 375-379
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Heparin-binding protein (HBP) is a potent inducer of increased vascular permeability. The purpose of this study was to examine plasma levels of HBP in patients with shock. DESIGN: Fifty-three consecutive patients with septic and non-septic shock at a mixed-bed intensive care unit were included, as well as 20 age-matched controls. Patients with local infections but without signs of shock served as infectious controls. Enzyme-linked immunosorbent assay was used to determine plasma levels of HBP. RESULTS: There were no differences in serum HBP levels between healthy controls and those with local infections, including urinary tract infections, pneumonia and gastroenteritis, without shock. Levels of HBP were higher in patients with non-septic shock and septic shock than healthy controls. However, there was no difference in serum HBP levels between patients with septic shock and those with non-septic shock. Moreover, HBP levels were not different between patients with low and high APACHE II scores. Plasma levels of HBP were similar in surviving and non-surviving patients with shock. CONCLUSIONS: HBP is elevated in patients with shock from septic and non-septic etiologies. Future investigations are required to define the functional role of HBP in patients with shock.
|
|
| 18. |
- Dickneite, Gerhard, et al.
(författare)
-
Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions
- 2015
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 113:4, s. 686-697
-
Forskningsöversikt (refereegranskat)abstract
- Coagulation Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of alpha(2)-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and alpha(v)beta(3) integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to. fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces-cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dys-regulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.
|
|
| 19. |
- Egesten, Arne, et al.
(författare)
-
A Leak in the Dike
- 2020
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 12:5, s. 355-356
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 20. |
- Egesten, Arne, et al.
(författare)
-
Catch me if you can or actors on the run
- 2018
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 11:1, s. 1-2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 21. |
- Egesten, Arne, et al.
(författare)
-
Going Fishing
- 2018
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:1, s. 1-2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 22. |
|
|
| 23. |
- Egesten, Arne, et al.
(författare)
-
Journal of Innate Immunity Ten Years Later
- 2018
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:5-6, s. 363-364
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 24. |
- Egesten, Arne, et al.
(författare)
-
Mast Cells and More
- 2021
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:3, s. 129-130
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 25. |
- Egesten, Arne, et al.
(författare)
-
Modelers Modelling Models
- 2021
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:2, s. 61-62
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
