1.
Kasetty, Gopinath, et al.
(author)
Osteopontin protects against lung injury caused by extracellular histones
2019
In: Mucosal Immunology. - : Elsevier BV. - 1933-0219 .- 1935-3456. ; 12:1, s. 39-50
Journal article (peer-reviewed) abstract
Extracellular histones are present in the airways because of cell death occurring during inflammation. They promote inflammation and cause tissue damage due to their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is expressed at high levels during airway inflammation and has been ascribed both pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may neutralize the harmful activities of extracellular histones at the airway mucosal surface. In a model of histone-induced acute lung injury, OPN−/− mice showed increased inflammation and tissue injury, and succumbed within 24 h, whereas wild-type mice showed lower degrees of inflammation and no mortality. In lipopolysaccharide-induced acute lung injury, wild-type mice showed less inflammation and tissue injury than OPN−/− mice. In bronchoalveolar lavage fluid from ARDS patients, high levels of OPN and also histone–OPN complexes were detected. In addition, OPN bound to histones with high affinity in vitro, resulting in less cytotoxicity and reduced formation of tissue-damaging neutrophil extracellular traps (NETs). The interaction between OPN and histones was dependent on posttranslational modification of OPN, i.e., phosphorylation. The findings demonstrate a novel role for OPN, modulating the pro-inflammatory and cytotoxic properties of free histones.
2.
Papareddy, Praveen, et al.
(author)
An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity
2018
In: Virulence. - : Informa UK Limited. - 2150-5608 .- 2150-5594. ; 9:1, s. 724-737
Journal article (peer-reviewed) abstract
Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity. Though all peptides tested executed bactericidal activity in mammalian plasma (with the exception of rodents), no killing was observed in plasma from birds, reptiles, and fish, pointing to a crucial role for the classical pathway of the complement system. We also observed an interference of these peptides with the human intrinsic pathway of coagulation though, unlike complement activation, this mechanism appears not to be evolutionary conserved.
3.
Tapper, Hans, et al.
(author)
Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles.
2002
In: Blood. - 0006-4971 .- 1528-0020. ; 99:5, s. 1785-93
Journal article (peer-reviewed) abstract
Human neutrophils have an important role in host defense against microbial infection. At different stages of an infectious process, neutrophils progressively up-regulate receptors and release various effector molecules. These are stored in several distinct types of granules with varying propensity to be secreted. Heparin-binding protein (HBP), also known as CAP37 or azurocidin, is a multifunctional, inactive serine-protease homologue. The present work shows that HBP is released from neutrophils on stimulation with secretagogues that do not trigger the secretion of azurophilic granule content. Therefore, the subcellular localization of HBP was investigated in more detail. Immunofluorescence microscopy revealed that HBP was localized close to the plasma membrane. Further analysis by fractionation of postnuclear supernatants from cavitated neutrophils showed that HBP is stored in azurophilic granules and secretory vesicles but that it is also detected to a minor extent in the plasma membrane. These findings were confirmed by immunoelectron microscopy showing that HBP colocalized with marker proteins of azurophilic granules and secretory vesicles. The presence of HBP in secretory vesicles possibly depends on the stage of cell differentiation, since the promyelocytic cell line HL-60 contains less HBP than mature neutrophils, stored exclusively in the less easily mobilized azurophilic granules. Our findings suggest that HBP can be synthesized or targeted to easily mobilized compartments at a late stage of neutrophil maturation. The ability of neutrophils to secrete HBP from secretory vesicles may be important for proinflammatory functions of this protein, such as the alteration of vascular permeability.
4.
Bengtson, Sara, et al.
(author)
Activation of TAFI on the Surface of Streptococcus pyogenes Evokes Inflammatory Reactions by Modulating the Kallikrein/Kinin System
2009
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 1:1, s. 18-28
Journal article (peer-reviewed) 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
5.
Berkestedt, Ingrid, et al.
(author)
Elevated Plasma Levels of Antimicrobial Polypeptides in Patients with Severe Sepsis.
2010
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:5, s. 478-482
Journal article (peer-reviewed) 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.
6.
Egesten, Arne, et al.
(author)
A Leak in the Dike
2020
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 12:5, s. 355-356
Journal article (other academic/artistic)
7.
Egesten, Arne, et al.
(author)
Going Fishing
2018
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:1, s. 1-2
Journal article (other academic/artistic)
8.
9.
Egesten, Arne, et al.
(author)
Modelers Modelling Models
2021
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:2, s. 61-62
Journal article (other academic/artistic)
10.
Egesten, Arne, et al.
(author)
Some Like It Hot
2021
In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:6, s. 321-322
Journal article (other academic/artistic)
