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Article ; Online: Transient Binding Dynamics of Complement System Pattern Recognition Molecules on Pathogens.

Götz, Maximilian Peter / Duque Villegas, Mario Alejandro / Fageräng, Beatrice / Kerfin, Aileen / Skjoedt, Mikkel-Ole / Garred, Peter / Rosbjerg, Anne

Journal of immunology (Baltimore, Md. : 1950)

2024 Volume 212, Issue 9, Page(s) 1493–1503

Abstract: Previous studies of pattern recognition molecules (PRMs) of the complement system have revealed difficulties in observing binding on pathogens such as Aspergillus fumigatus and Escherichia coli, despite complement deposition indicative of classical and ... ...

Abstract	Previous studies of pattern recognition molecules (PRMs) of the complement system have revealed difficulties in observing binding on pathogens such as Aspergillus fumigatus and Escherichia coli, despite complement deposition indicative of classical and lectin pathway activation. Thus, we investigated the binding dynamics of PRMs of the complement system, specifically C1q of the classical pathway and mannose-binding lectin (MBL) of the lectin pathway. We observed consistently increasing deposition of essential complement components such as C4b, C3b, and the terminal complement complex on A. fumigatus and E. coli. However, C1q and MBL binding to the surface rapidly declined during incubation after just 2-4 min in 10% plasma. The detachment of C1q and MBL can be linked to complement cascade activation, as the PRMs remain bound in the absence of plasma. The dissociation and the fate of C1q and MBL seem to have different mechanistic functions. Notably, C1q dynamics were associated with local C1 complex activation. When C1s was inhibited in plasma, C1q binding not only remained high but further increased over time. In contrast, MBL binding was inversely correlated with total and early complement activation due to MBL binding being partially retained by complement inhibition. Results indicate that detached MBL might be able to functionally rebind to A. fumigatus. In conclusion, these results reveal a (to our knowledge) novel "hit-and-run" complement-dependent PRM dynamic mechanism on pathogens. These dynamics may have profound implications for host defense and may help increase the functionality and longevity of complement-dependent PRMs in circulation.
MeSH term(s)	Complement C1q ; Escherichia coli/metabolism ; Mannose-Binding Lectin/metabolism ; Complement System Proteins ; Complement Activation ; Lectins/metabolism ; Complement Pathway, Mannose-Binding Lectin
Chemical Substances	Complement C1q (80295-33-6) ; Mannose-Binding Lectin ; Complement System Proteins (9007-36-7) ; Lectins
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300768
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Article ; Online: MASP-1 and MASP-3 Bind Directly to Aspergillus fumigatus and Promote Complement Activation and Phagocytosis.

Rosbjerg, Anne / Würzner, Reinhard / Garred, Peter / Skjoedt, Mikkel-Ole

Journal of innate immunity

2021 Volume 13, Issue 4, Page(s) 211–224

Abstract: Activation of the complement system is mediated by the interaction between pathogens and pattern recognition molecules (PRMs); mannose-binding lectin (MBL), ficolins, and collectin-10/-11 from the lectin pathway and C1q from the classical pathway. Lectin ...

Abstract	Activation of the complement system is mediated by the interaction between pathogens and pattern recognition molecules (PRMs); mannose-binding lectin (MBL), ficolins, and collectin-10/-11 from the lectin pathway and C1q from the classical pathway. Lectin pathway activation specifically depends on proteases named MBL-associated serine proteases (MASPs) that are found in complexes with PRMs. In this study, we hypothesize that MASPs can recognize selected pathogens independently of PRMs. Using different clinical strains of opportunistic fungi, we have observed that MASPs directly recognize certain fungal pathogens in a way that can facilitate complement activation. Among these were Aspergillus fumigatus - a dangerous pathogen, especially for immunocompromised patients. In flow cytometry and fluorescence microscopy, we found that MASP-1 and -3 bound to all A. fumigatus growth stages (conidia, germ tubes, and hyphae), whereas rMASP-2 and the nonproteolytic rMAP-1 did not. Bound rMASPs could recruit rMBL and rficolin-3 to A. fumigatus conidia in a nonclassical manner and activate complement via rMASP-2. In experiments using recombinant and purified components, rMASP-1 increased the neutrophilic phagocytosis of conidia. In serum where known complement activation pathways were blocked, phagocytosis could be mediated by rMASP-3. We have encountered an unknown pathway for complement activation and found that MASP-1 and MASP-3 have dual functions as enzymes and as PRMs.
MeSH term(s)	Aspergillus fumigatus ; Complement Activation ; Complement Pathway, Mannose-Binding Lectin ; Complement System Proteins ; Humans ; Mannose-Binding Lectin ; Mannose-Binding Protein-Associated Serine Proteases ; Phagocytosis
Chemical Substances	Mannose-Binding Lectin ; Complement System Proteins (9007-36-7) ; MASP1 protein, human (EC 3.4.21.-) ; Mannose-Binding Protein-Associated Serine Proteases (EC 3.4.21.-)
Language	English
Publishing date	2021-03-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454158-8
ISSN	1662-8128 ; 1662-811X
ISSN (online)	1662-8128
ISSN	1662-811X
DOI	10.1159/000514546
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Article ; Online: Functional Analysis of a Novel Complement C5a Receptor 1-Blocking Monoclonal Antibody.

Cyranka, Leon / Mariegaard, Ida / Skjødt, Mikkel-Ole / Bayarri-Olmos, Rafael / Mollnes, Tom Eirik / Garred, Peter / Rosbjerg, Anne

Journal of innate immunity

2023 Volume 15, Issue 1, Page(s) 836–849

Abstract: Introduction: The complement system anaphylatoxin C5a is a critical player in inflammation. By binding to complement C5a receptor 1 (C5aR1/CD88), C5a regulates many cellular functions, mainly as a potent pro-inflammatory inducer. We describe the ... ...

Abstract	Introduction: The complement system anaphylatoxin C5a is a critical player in inflammation. By binding to complement C5a receptor 1 (C5aR1/CD88), C5a regulates many cellular functions, mainly as a potent pro-inflammatory inducer. We describe the generation and selection of a potent antagonistic C5aR1 mouse monoclonal antibody (mAb). Methods: Initial C5aR1 hybridoma clone selection was performed with a cell-binding study in human whole blood. In-house C5aR1 mAb assessment for C5aR1 inhibition was done via the iLite® C5a assay. C5aR1 mAb specificity was investigated on C5aR1his- and C5aR2his-expressing Flp-In™-CHO cells. Physiological C5aR1 inhibition was assessed via a C5a-driven calcium flux assay and stimulation assay based on isolated polymorphonuclear leukocytes (PMNs) and a whole blood model stimulated with Escherichia coli. Results: The supernatant of hybridoma clones targeting the N-terminal section of C5aR1 displayed efficient binding to C5aR1 in whole blood, which was confirmed for purified mAbs. The C5aR1 mAb 18-41-6 was selected following the assay of in-house C5aR1 mAbs via the iLite® C5a assay. The mAb 18-41-6 was specific for C5aR1. Full-size and/or F(ab')2 preparations of mAb 18-41-6 were found to efficiently abrogate C5a-induced calcium flux in neutrophils and to significantly reduce the upregulation of the activation markers CD11b (neutrophils, monocytes) and CD66b (neutrophils). Conclusion: Our results demonstrate that mAb 18-41-6 is a valuable tool for investigating the C5a-C5aR1 axis and a potential therapeutic candidate for inflammatory disease treatment.
MeSH term(s)	Cricetinae ; Animals ; Mice ; Humans ; Antibodies, Monoclonal ; Cricetulus ; Calcium ; Complement C5a/metabolism ; Signal Transduction ; Receptor, Anaphylatoxin C5a
Chemical Substances	Antibodies, Monoclonal ; Calcium (SY7Q814VUP) ; Complement C5a (80295-54-1) ; Receptor, Anaphylatoxin C5a
Language	English
Publishing date	2023-11-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2454158-8
ISSN	1662-8128 ; 1662-811X
ISSN (online)	1662-8128
ISSN	1662-811X
DOI	10.1159/000535084
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Article ; Online: Complement C7 and clusterin form a complex in circulation.

Massri, Mariam / Toonen, Erik J M / Sarg, Bettina / Kremser, Leopold / Grasse, Marco / Fleischer, Verena / Torres-Quesada, Omar / Hengst, Ludger / Skjoedt, Mikkel-Ole / Bayarri-Olmos, Rafael / Rosbjerg, Anne / Garred, Peter / Orth-Höller, Dorothea / Prohászka, Zoltán / Würzner, Reinhard

Frontiers in immunology

2024 Volume 15, Page(s) 1330095

Abstract: Introduction: The complement system is part of innate immunity and is comprised of an intricate network of proteins that are vital for host defense and host homeostasis. A distinct mechanism by which complement defends against invading pathogens is ... ...

Abstract	Introduction: The complement system is part of innate immunity and is comprised of an intricate network of proteins that are vital for host defense and host homeostasis. A distinct mechanism by which complement defends against invading pathogens is through the membrane attack complex (MAC), a lytic structure that forms on target surfaces. The MAC is made up of several complement components, and one indispensable component of the MAC is C7. The role of C7 in MAC assembly is well documented, however, inherent characteristics of C7 are yet to be investigated. Methods: To shed light on the molecular characteristics of C7, we examined the properties of serum-purified C7 acquired using polyclonal and novel monoclonal antibodies. The properties of serum‑purified C7 were investigated through a series of proteolytic analyses, encompassing Western blot and mass spectrometry. The nature of C7 protein-protein interactions were further examined by a novel enzyme-linked immunosorbent assay (ELISA), as well as size‑exclusion chromatography. Results: Protein analyses showcased an association between C7 and clusterin, an inhibitory complement regulator. The distinct association between C7 and clusterin was also demonstrated in serum-purified clusterin. Further assessment revealed that a complex between C7 and clusterin (C7-CLU) was detected. The C7-CLU complex was also identified in healthy serum and plasma donors, highlighting the presence of the complex in circulation. Discussion: Clusterin is known to dissociate the MAC structure by binding to polymerized C9, nevertheless, here we show clusterin binding to the native form of a terminal complement protein in vivo. The presented data reveal that C7 exhibits characteristics beyond that of MAC assembly, instigating further investigation of the effector role that the C7-CLU complex plays in the complement cascade.
MeSH term(s)	Complement C7/metabolism ; Clusterin ; Complement System Proteins/metabolism ; Complement Membrane Attack Complex/metabolism ; Complement Activation
Chemical Substances	Complement C7 ; Clusterin ; Complement System Proteins (9007-36-7) ; Complement Membrane Attack Complex
Language	English
Publishing date	2024-01-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1330095
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Article ; Online: Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes.

Jarlhelt, Ida / Pilely, Katrine / Clausen, Jytte Bryde / Skjoedt, Mikkel-Ole / Bayarri-Olmos, Rafael / Garred, Peter

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 204, Issue 7, Page(s) 1919–1928

Abstract: The complement system constitutes an important part of the innate immune system. The collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. During previous experiments with ... ...

Abstract	The complement system constitutes an important part of the innate immune system. The collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. During previous experiments with ficolin-2 and ficolin-3, we have observed that the molecules may interact. We therefore hypothesized the existence of stable ficolin-2/-3 heterocomplexes. We could demonstrate ficolin-2/-3 heterocomplexes in normal human serum and plasma by ELISA using Abs specific for ficolin-2 and ficolin-3. The formation of heteromeric protein complexes were validated by coimmunoprecipitation and Western blot analysis. When recombinant ficolin-2 and recombinant ficolin-3 were mixed, no complexes were formed. However, when coexpressing ficolin-2 and ficolin-3 in Chinese hamster ovary cells, we could detect ficolin-2/-3 heterocomplexes in the supernatant. Furthermore, we measured concentration of the ficolin-2/-3 heterocomplexes in arbitrary units in 94 healthy individuals. We also established the relationship between the concentrations of ficolin-2, ficolin-3, and the ficolin-2/-3 heterocomplexes. We observed that the concentration of the ficolin-2/-3 heterocomplex correlated significantly with ficolin-2 (ρ: 0.24,
MeSH term(s)	Animals ; CHO Cells ; Cell Line ; Collectins/metabolism ; Complement Activation/physiology ; Complement Pathway, Mannose-Binding Lectin/physiology ; Complement System Proteins/metabolism ; Cricetulus ; Humans ; Lectins/blood ; Mannose-Binding Protein-Associated Serine Proteases/metabolism ; Mice ; Ficolins
Chemical Substances	Collectins ; FCN3 protein, human ; Lectins ; Complement System Proteins (9007-36-7) ; Mannose-Binding Protein-Associated Serine Proteases (EC 3.4.21.-)
Language	English
Publishing date	2020-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1900694
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Article: The ficolin response to LPS challenge in mice

Jarlhelt, Ida / Garred, Peter / Genster, Ninette / Kirketerp-Møller, Nikolaj / Skjoedt, Mikkel-Ole

Molecular immunology. 2019 Apr., v. 108

2019

Abstract: The ficolins belong to an important family of pattern recognition molecules, which contributes to complement activation via the lectin pathway. How the ficolins respond to inflammatory stimuli remains only partly understood. In the present study, we ... ...

Abstract	The ficolins belong to an important family of pattern recognition molecules, which contributes to complement activation via the lectin pathway. How the ficolins respond to inflammatory stimuli remains only partly understood. In the present study, we investigated the ficolin A and ficolin B expression and protein distribution patterns in a mouse model of LPS-induced inflammation. The time- and tissue-specific expression of ficolin A and B was determined by real time PCR. Furthermore, ficolin protein levels in serum and bone marrow extracts from LPS challenged mice were determined by novel in-house developed sandwich ELISAs. Ficolin A was mainly expressed in liver and spleen. However, our data also suggested that ficolin A is expressed in bone marrow, which is the main site of ficolin B expression. The level of ficolin A and B expression was increased after stimulation with LPS in the investigated tissues. This was followed by a downregulation of expression, causing mRNA levels to return to baseline 24 h post LPS challenge. Protein levels appeared to follow the same pattern as the expression profiles, with an exception of ficolin B levels in serum, which kept increasing for 24 h. Ficolin A was likewise significantly increased in bronchoalveolar lavage fluid from mice infected with the fungi A. fumigatus, pointing towards a similar effect of the ficolins in non-sterile mouse models of inflammation. The results demonstrate that LPS-induced inflammation can induce a significant ficolin response, suggesting that the murine ficolins are acute phase reactants with increase in both mRNA expression and protein levels during systemic inflammation.
Keywords	acute phase proteins ; animal models ; blood serum ; bone marrow ; enzyme-linked immunosorbent assay ; fungi ; gene expression ; gene expression regulation ; inflammation ; lectins ; liver ; messenger RNA ; mice ; protein content ; quantitative polymerase chain reaction ; spleen
Language	English
Dates of publication	2019-04
Size	p. 121-127.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2019.02.013
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The SARS-CoV-2 Y453F mink variant displays a pronounced increase in ACE-2 affinity but does not challenge antibody neutralization.

Bayarri-Olmos, Rafael / Rosbjerg, Anne / Johnsen, Laust Bruun / Helgstrand, Charlotte / Bak-Thomsen, Theresa / Garred, Peter / Skjoedt, Mikkel-Ole

The Journal of biological chemistry

2021 Volume 296, Page(s) 100536

Abstract: Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from humans to animals has been reported for many domesticated species, including farmed minks. The identification of novel spike gene mutations appearing in minks has raised major concerns ... ...

Abstract	Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from humans to animals has been reported for many domesticated species, including farmed minks. The identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. One genetic variant, known as "cluster five," arose among farmed minks in Denmark and resulted in a complete shutdown of the world's largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the cluster-five variant, which contains a mutation resulting in a Y453F residue change in the receptor-binding domain (RBD) of the spike protein. Using an ELISA-based angiotensin-converting enzyme-2/RBD inhibition assay, we show that the Y453F variant does not decrease established humoral immunity from previously infected individuals or affect the neutralizing antibody response in a vaccine mouse model based on the original Wuhan strain RBD or spike as antigens. However, biolayer interferometry analysis demonstrates that it binds the human angiotensin-converting enzyme-2 receptor with a 4-fold higher affinity than the original strain, suggesting an enhanced transmission capacity and a possible challenge for viral control. These results also indicate that the rise in the frequency of the cluster-five variant in mink farms might be a result of the fitness advantage conferred by the receptor adaptation rather than evading immune responses.
MeSH term(s)	Amino Acid Substitution ; Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/immunology ; Animals ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/metabolism ; Antibodies, Viral/chemistry ; Antibodies, Viral/metabolism ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/transmission ; Convalescence ; Denmark/epidemiology ; Gene Expression ; HEK293 Cells ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immune Sera/chemistry ; Immunity, Innate ; Mink/virology ; Models, Molecular ; Mutation ; Pandemics ; Protein Binding ; Protein Structure, Secondary ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Virus Internalization
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immune Sera ; Recombinant Proteins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100536
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Article ; Online: Reply to Lassaunière: On the functional characterization of the Y453F RBD variant found in cluster 5 SARS-CoV-2.

Bayarri-Olmos, Rafael / Johnsen, Laust Bruun / Rosbjerg, Anne / Helgstrand, Charlotte / Bak-Thomsen, Theresa / Garred, Peter / Skjoedt, Mikkel-Ole

The Journal of biological chemistry

2021 Volume 297, Issue 5, Page(s) 101241

MeSH term(s)	Antibodies, Neutralizing ; COVID-19 ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.101241
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Article ; Online: The ficolin response to LPS challenge in mice.

Jarlhelt, Ida / Genster, Ninette / Kirketerp-Møller, Nikolaj / Skjoedt, Mikkel-Ole / Garred, Peter

Molecular immunology

2019 Volume 108, Page(s) 121–127

Abstract	The ficolins belong to an important family of pattern recognition molecules, which contributes to complement activation via the lectin pathway. How the ficolins respond to inflammatory stimuli remains only partly understood. In the present study, we investigated the ficolin A and ficolin B expression and protein distribution patterns in a mouse model of LPS-induced inflammation. The time- and tissue-specific expression of ficolin A and B was determined by real time PCR. Furthermore, ficolin protein levels in serum and bone marrow extracts from LPS challenged mice were determined by novel in-house developed sandwich ELISAs. Ficolin A was mainly expressed in liver and spleen. However, our data also suggested that ficolin A is expressed in bone marrow, which is the main site of ficolin B expression. The level of ficolin A and B expression was increased after stimulation with LPS in the investigated tissues. This was followed by a downregulation of expression, causing mRNA levels to return to baseline 24 h post LPS challenge. Protein levels appeared to follow the same pattern as the expression profiles, with an exception of ficolin B levels in serum, which kept increasing for 24 h. Ficolin A was likewise significantly increased in bronchoalveolar lavage fluid from mice infected with the fungi A. fumigatus, pointing towards a similar effect of the ficolins in non-sterile mouse models of inflammation. The results demonstrate that LPS-induced inflammation can induce a significant ficolin response, suggesting that the murine ficolins are acute phase reactants with increase in both mRNA expression and protein levels during systemic inflammation.
MeSH term(s)	Animals ; Aspergillosis/immunology ; Aspergillosis/microbiology ; Aspergillus fumigatus/pathogenicity ; Biological Assay ; Bone Marrow/drug effects ; Bone Marrow/metabolism ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Lectins/blood ; Lectins/metabolism ; Lipopolysaccharides/pharmacology ; Mice ; Organ Specificity/drug effects ; Reproducibility of Results ; Ficolins
Chemical Substances	Lectins ; Lipopolysaccharides
Language	English
Publishing date	2019-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2019.02.013
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Article ; Online: Combining MAP-1:CD35 or MAP-1:CD55 fusion proteins with pattern-recognition molecules as novel targeted modulators of the complement cascade.

Pérez-Alós, Laura / Bayarri-Olmos, Rafael / Skjoedt, Mikkel-Ole / Garred, Peter

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2019 Volume 33, Issue 11, Page(s) 12723–12734

Abstract: Dysregulation of the complement system is involved in the pathogenesis of several diseases, and its inhibition has been shown to be a feasible therapeutic option. Therefore, there is an interest in the development of complement modulators to treat ... ...

Abstract	Dysregulation of the complement system is involved in the pathogenesis of several diseases, and its inhibition has been shown to be a feasible therapeutic option. Therefore, there is an interest in the development of complement modulators to treat complement activation-related inflammatory pathologies. Mannose-binding lectin (MBL)/ficolin/collectin-associated protein-1 (MAP-1) is a regulatory molecule of the lectin pathway (LP), whereas complement receptor 1 (CD35) and decay-accelerating factor (CD55) are membrane-anchored regulators with effects on the central effector molecule C3. In this study, we developed 2 novel soluble chimeric inhibitors by fusing MAP-1 to the 3 first domains of CD35 (CD35
MeSH term(s)	Adaptor Proteins, Signal Transducing/chemistry ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/pharmacology ; Animals ; Apoptosis Regulatory Proteins/chemistry ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/pharmacology ; CD55 Antigens/chemistry ; CD55 Antigens/genetics ; CD55 Antigens/pharmacology ; CHO Cells ; Complement Activation/drug effects ; Complement C3/chemistry ; Complement C3/metabolism ; Cricetulus ; Humans ; Receptors, Complement 3b/chemistry ; Receptors, Complement 3b/genetics ; Receptors, Pattern Recognition/chemistry ; Receptors, Pattern Recognition/genetics ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/pharmacology
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; CD55 Antigens ; CR1 protein, human ; Complement C3 ; MOAP1 protein, human ; Receptors, Complement 3b ; Receptors, Pattern Recognition ; Recombinant Fusion Proteins
Language	English
Publishing date	2019-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201901643R
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