| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Andersson, E., et al.
(författare)
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Isolation of human cationic antimicrobial protein-18 from seminal plasma and its association with prostasomes.
- 2002
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 17:10, s. 34-2529
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cathelicidins are a group of antibiotic peptides with broad antimicrobial activity. They are considered to be an essential part of the innate immune system. The only known human cathelicidin is the human cationic antimicrobial protein (hCAP-18), from which the antimicrobial peptide LL-37 is released. METHODS AND RESULTS: In the present study, we purified hCAP-18 from seminal plasma and confirmed its identity by N-terminal amino acid sequencing. Gel filtration of seminal plasma showed the presence of hCAP-18 in both a low and a high molecular weight peak. Fractions corresponding to the high molecular form of hCAP-18 also contained dipeptidyl peptidase IV (CD26), a prostasome marker. This finding suggested that hCAP-18 found in fractions corresponding to high molecular weight molecules, is prostasome-associated. Flow cytometry confirmed the association of hCAP-18 with prostasomes and indicated that the molecule is surface bound. Western blot showed the presence of intact hCAP-18 in sperm, prostasomes and ultracentrifuged seminal plasma. CONCLUSIONS: These findings suggest that hCAP-18 may have an important role in antimicrobial defence during human reproduction. The binding of hCAP-18 to prostasomes indicates that protasomes can serve as a reservoir of this precursor of the antibiotic peptide LL-37.
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| 4. |
- Borregaard, N, et al.
(författare)
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Neutrophils and keratinocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place
- 2005
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Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 77:4, s. 439-443
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Tidskriftsartikel (refereegranskat)abstract
- The human neutrophil is a professional phagocyte of fundamental importance for defense against microorganisms, as witnessed by the life-threatening infections occurring in patients with neutropenia or with defects that result in decreased microbicidal activity of the neutrophil [1, 2]. Likewise, the skin and mucosal surfaces provide important barriers against infections. Traditionally, these major defense systems, the epithelial cells and the neutrophils, have been viewed as limited in their armory: The epithelial cells provide defense by constituting a physical barrier, and the neutrophils provide instant delivery of preformed antimicrobial substances or on-the-spot assembly of the multicomponent reduced nicotinamide adenine dinucleotide phosphate oxidase from stored components for the generation of reactive oxygen metabolites. Recent research has shown that epithelial cells are highly dynamic and able to generate antimicrobial peptides in response not only to microbial infection itself [3–6] but more importantly, to the growth factors that are called into play when the physical barrier is broken, and the risk of microbial infection is imminent [7]. Likewise, the neutrophil changes its profile of actively transcribed genes when it diapedeses into wounded skin [8]. This results in generation of signaling molecules, some of which support the growth and antimicrobial potential of keratinocytes and epithelial cells. This paper will highlight some recent advances in this field.
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| 5. |
- Borregaard, N, et al.
(författare)
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Regulation of human neutrophil granule protein expression
- 2001
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 8:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- The function of the mature polymorphonuclear neutrophil is dependent on its granules, each with its characteristic content of proteins. The granule proteins are formed at different stages during maturation of neutrophils from myeloblasts to segmented cells. The regulation of granule protein expression is controlled by a number of transcription factors, many of which are also essential for commitment of multipotent hematopoietic stem cells to lineage-committed myeloid progenitor cells and for differentiation of these progenitor cells; among these, PU.1 and C/EBPalpha stand out as critical for all granule proteins whereas AML-1 is critical for primary granule protein expression and C/EBPepsilon for secondary and tertiary granule protein expression.
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| 6. |
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| 7. |
- Clemmensen, SN, et al.
(författare)
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Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis
- 2011
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Ingår i: EUROPEAN JOURNAL OF HAEMATOLOGY. - 0902-4441. ; 86:6, s. 517-530
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated with azurophile granules in neutrophils indicative of A1AT expression being restricted to the promyelocyte stage. We examined the localization and production of A1AT in healthy donor neutrophils and found A1AT to be a constituent of all granule subtypes and to be released from neutrophils following stimulation. A1AT is produced at all stages of myeloid maturation in the bone marrow. The production increases as neutrophils enter circulation and increases further upon migration to tissues as observed in skin windows and when blood neutrophils are incubated with granulocyte colony-stimulating factor. Neutrophils from patients with A1AT-deficiency carrying the (PI)ZZ mutation in the A1AT gene appeared structurally and functionally normal, but A1AT produced in leukocytes of these patients lacked the ability to bind proteases efficiently. We conclude that A1AT generation and release from neutrophils add significantly to the antiprotease levels in tissues during inflammation. Impaired binding of neutrophil A1AT to serine proteases in patients with (PI)ZZ mutations may enhance their susceptibility to the development of emphysema.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Lauck, S. B., et al.
(författare)
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Accelerating knowledge translation to improve cardiovascular outcomes and health services: opportunities for bridging science and clinical practice
- 2023
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Ingår i: European Journal of Cardiovascular Nursing. - 1474-5151 .- 1873-1953. ; 22:8
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge translation (KT) is the exchange between knowledge producers and users to understand, synthesize, share, and apply evidence to accelerate the benefits of research to improve health and health systems. Knowledge translation practice (activities/strategies to move evidence into practice) and KT science (study of the methodology and approaches to promote the uptake of research) benefit from the use of conceptual thinking, the meaningful inclusion of patients, and the application of intersectionality. In spite of multiple barriers, there are opportunities to develop strong partnerships and evidence to drive an impactful research agenda and increase the uptake of cardiovascular research.
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| 12. |
- Lögdberg, Bengt, et al.
(författare)
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Lipocalins in clinical medicine
- 2006
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Ingår i: Lipocalins. - 9781587062971 ; , s. 187-187
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Bokkapitel (populärvet., debatt m.m.)
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| 13. |
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| 14. |
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| 15. |
- Marstrand, T. T., et al.
(författare)
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A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia
- 2010
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 24:7, s. 1265-1275
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges as a consequence of the t(15;17) translocation, acts as a transcriptional repressor that blocks neutrophil differentiation at the promyelocyte (PM) stage. In this study, we used publicly available microarray data sets and identified signatures of genes dysregulated in APL by comparison of gene expression profiles of APL cells and normal PMs representing the same stage of differentiation. We next subjected our identified APL signatures of dysregulated genes to a series of computational analyses leading to (i) the finding that APL cells show stem cell properties with respect to gene expression and transcriptional regulation, and (ii) the identification of candidate drugs and drug targets for therapeutic interventions. Significantly, our study provides a conceptual framework that can be applied to any subtype of AML and cancer in general to uncover novel information from published microarray data sets at low cost. In a broader perspective, our study provides strong evidence that genomic strategies might be used in a clinical setting to prospectively identify candidate drugs that subsequently are validated in vitro to define the most effective drug combination for individual cancer patients on a rational basis. Leukemia (2010) 24, 1265-1275; doi:10.1038/leu.2010.95; published online 27 May 2010
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| 16. |
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| 17. |
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| 18. |
- Sorensen, OE, et al.
(författare)
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Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin - A novel mechanism of generating antimicrobial peptides in vagina
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:31, s. 28540-28546
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Tidskriftsartikel (refereegranskat)abstract
- The human cathelicidin, hCAP-18, is expressed both in neutrophils and in epithelial cells. hCAP-18 is processed to the antimicrobial peptide LL-37 by proteinase 3 in neutrophils. hCAP-18 is highly expressed in the epididymis with a subsequent high concentration in seminal plasma where the protein is present in its unprocessed and antimicrobially inactive form. We report here that hCAP-18 in seminal plasma is processed to generate a 38-amino acid antimicrobial peptide ALL-38 by the prostate-derived protease gastricsin when incubated at a pH corresponding to the vaginal pH. In accordance with this, seminal plasma derived hCAP-18 was found in its processed form in the vagina following sexual intercourse. The antimicrobial activity of ALL-38 against a variety of microorganisms tested is equal to that of LL37. This enzymatic activation of a proantimicrobial substance in seminal plasma following exposure to the vaginal milieu represents a novel mechanism to prevent infection following sexual intercourse.
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| 19. |
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| 20. |
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| 21. |
- Sørensen, Ole E, et al.
(författare)
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Cathelicidins - Nature's attempt at combinatorial chemistry
- 2005
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Ingår i: Combinatorial Chemistry & High Throughput Screening. - : Bentham Science Publishers Ltd.. - 1386-2073. ; 8:3, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- Cathelicidins are a family of diverse antimicrobial peptides found in granules of mammalian neutrophils. Cathelicidins are active against a broad range of microbes in different environments. Aside from their antimicrobial activity, cathelicidins possess other biological properties including cytotoxic activity towards mammalian cells. Several studies have shown that the amino acid sequence of cathelicidins can be modified to temper undesired properties, such as hemolytic and cytotoxic activity, and at the same time maintain antimicrobial activity. These properties make cathelicidins ideal templates in combinatorial chemistry for designing de novo antimicrobial peptides for therapeutic use. However, one of the major challenges will be to screen these peptides in experimentally relevant models that reflect the environments in which the peptides should be therapeutically active.
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| 22. |
- Sørensen, Ole E, et al.
(författare)
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Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3
- 2001
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 97:12, s. 3951-3959
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Tidskriftsartikel (refereegranskat)abstract
- Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species.
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| 23. |
- Sørensen, Ole E, et al.
(författare)
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Papillon-Lefevre syndrome patient reveals species-dependent requirements for neutrophil defenses
- 2014
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 124:10, s. 4539-4548
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Tidskriftsartikel (refereegranskat)abstract
- Papillon-Lefevre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18. into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.
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| 24. |
- Udby, L, et al.
(författare)
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beta-Microseminoprotein binds CRISP-3 in human seminal plasma
- 2005
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 333:2, s. 555-561
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Tidskriftsartikel (refereegranskat)abstract
- P-Microseminoprotein (MSP) and cysteine-rich secretory protein 3 (CRISP-3) are abundant constituents of human seminal plasma. Immunoprecipitation and gel filtration of seminal plasma proteins combined with examination of the proteins in their pure form showed that MSP and CRISP-3 form stable, non-covalent complexes. CRISP-3 binds MSP with very high affinity, as evidenced by surface plasmon resonance. Due to far higher abundance of MSP in prostatic fluid, it manifests large overcapacity for CRISP-3 binding. Structural similarity with an MSP-binding protein from blood plasma suggests that CRISP-3 binds MSP through its ami-terminal SCP-domain.
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| 25. |
- Udby, L, et al.
(författare)
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Characterization and localization of cysteine-rich secretory protein 3 (CRISP-3) in the human male reproductive tract
- 2005
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Ingår i: Journal of Andrology. - : Wiley. - 0196-3635. ; 26:3, s. 333-342
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian members of the cysteine-rich secretory protein (CRISP) family are expressed predominantly in the male reproductive tract and are implicated in the process of reproduction from spermiogenesis, posttesticular sperm maturation, and capacitation to oocyte-sperm fusion, and possibly also penetration of the zona pellucida. Rodents express only 2 CRISPs (CRISP-1 and CRISP-2) in their male reproductive system, whereas humans and horses express an additional third member named CRISP-3. We have previously demonstrated that this protein is present in human seminal plasma as well as in other exocrine secretions, in blood plasma, and in neutrophilic granulocytes. To characterize the protein in seminal plasma and localize the production of CRISP-3 in the human male reproductive tract, we performed immunoblotting and enzyme-linked immunosorbent assay measurements of seminal plasma and immunohistochemistry and in situ hybridization of tissue specimens. We were able to show that human CRISP-3 is a quantitatively minor seminal plasma protein not associated with prostasomes. Furthermore, CRISP-3 expression was found in the secretory epithelium throughout the male genital tract, with particularly high expression in the cauda epididymis and ampulla vas deferens. Examination of seminal plasma from vasectomized males indicates that organs downstream of the epididymis are probably the major sources of seminal plasma CRISP-3.
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| 26. |
- Ye, Y, et al.
(författare)
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The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 11685-
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Tidskriftsartikel (refereegranskat)abstract
- The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency and in conditions in which bone marrow myelopoiesis is negatively affected.
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| 27. |
- Åkerström, Bo, et al.
(författare)
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Alpha(1)-microglobulin.
- 2006
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Ingår i: Lipocalins. - 1587062976 ; , s. 110-110
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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