A5048940037- Complement system in diseases
- Reproductive tract infections research
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Adenosine and Purinergic Signaling
- Reproductive System and Pregnancy
- Neuropeptides and Animal Physiology
- Urinary Tract Infections Management
- Asthma and respiratory diseases
- Blood Coagulation and Thrombosis Mechanisms
- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Blood groups and transfusion
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Sepsis Diagnosis and Treatment
- Acute Kidney Injury Research
- Reproductive Physiology in Livestock
- Inflammasome and immune disorders
- Clostridium difficile and Clostridium perfringens research
- Drug Transport and Resistance Mechanisms
- Inhalation and Respiratory Drug Delivery
- Lipid Membrane Structure and Behavior
- Radiopharmaceutical Chemistry and Applications
Medizinische Hochschule Hannover
2014-2024
University of Hagen
2021
University of Tübingen
2017
University of Sheffield
2013
Institute of Medical Microbiology and Hygiene
1988-2011
Czech Academy of Sciences, Institute of Microbiology
1998-2004
Institut für Medizinische Informatik, Biometrie und Epidemiologie
1993
University of Lausanne
1988
Johannes Gutenberg University Mainz
1988
Abstract The complement system as well the coagulation has fundamental clinical implications in context of life-threatening tissue injury and inflammation. Associations between both cascades have been proposed, but precise molecular mechanisms remain unknown. current study reports multiple links for various factors fibrinolysis with central components C3 C5 vitro ex vivo. Thrombin, human (F) XIa, Xa, IXa, plasmin were all found to effectively cleave C5. Mass spectrometric analyses identified...
The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for human adaptive immune cells has not been described. We found that the assembles CD4(+) T and initiates caspase-1-dependent secretion, thereby promoting interferon-γ production helper 1 (T(H)1) differentiation an autocrine fashion. assembly requires intracellular C5 activation stimulation of C5a receptor (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant...
SCCM Pediatric Critical Care Medicine Explorations
Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside host cell. Chlamydial infection has been shown to protect the cell against apoptotic stimuli. This is likely important for ability of reproduce human cells. Here we show resistance apoptosis conveyed by destruction proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad during infection. Apoptotic stimuli were blocked upstream mitochondrial activation Bax/Bak. During with both species, trachomatis pneumoniae, Bim...
The anaphylatoxin C3a is a potent chemotactic peptide and inflammatory mediator released during complement activation which binds to activates G-protein-coupled receptor. Molecular cloning of the C3aR has facilitated studies identify nonpeptide antagonists C3aR. A chemical lead that selectively inhibited in high throughput screen was identified chemically optimized. resulting antagonist, N(2)-[(2,2-diphenylethoxy)acetyl]-L-arginine (SB 290157), functioned as competitive antagonist (125)I-C3a...
Abstract A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared U‐937 cells which had been differentiated with dibutyryl cAMP to macrophage‐like phenotype. The contained an insert of 4.3 kbp and able confer transfected HEK‐293 capacity bind specifically iodinated C3a. Chinese hamster ovary co‐transfected this G‐protein alpha subunit (Gα‐16) became functionally responsive analog synthetic peptide, as measured by increased...
The pathophysiological relevance of the complement split product C3a as a proinflammatory mediator is still ill defined. expression pattern human receptor (C3aR) can provide important clues for role this anaphylatoxin in inflammation. There strong evidence C3aR on basophils, and eosinophils, but additionally, only tumor cell lines leukemic or hepatic origin. It unclear whether neutrophils also express C3aR, need costimulus provided by eosinophils certain biological responses, lack respond to...
Abstract A C5a-receptor antagonist was selected from human C5a phage display libraries in which the C terminus of des-Arg74-hC5a mutated. The molecule is a competitive receptor vitro and vivo. Signal transduction interrupted at level G-protein activation. In addition, does not cause any phosphorylation. Proinflammatory properties such as chemotaxis or lysosomal enzyme release differentiated U937 cells, well C5a-induced changes intracellular Ca2+ concentration murine peritoneal macrophages,...
C5L2 is a 7 transmembrane domain receptor for complement fragment C5a that, unlike the classical receptor, C5aR, does not couple to G proteins. However, in mice where has been deleted, response altered, suggesting that may have signaling function. In order investigate whether human also some capacity transduce signals, we attempted produce competent form of by inserting C5aR sequences at three key protein activation motifs. detected neither an intracellular Ca(2+) nor beta-arrestin...
Objective To investigate protein complement 3a (C3a) and 3 (C3) plasma levels in trauma patients directly after the injury, relation to patients' outcome, development of sepsis, or injury severity, as determined by either Polytrauma Score (PTS), Injury Severity (ISS), Trauma (TRISS). Design Prospective study. Setting Surgical intensive care unit a university hospital. Patients Thirty-four with multiple trauma. Interventions None. Measurements Main Results C3a C3 concentrations, well C3a/C3...
Immune complex (IC)-induced inflammation is integral to the pathogenesis of several autoimmune diseases. ICs activate complement system and interact with IgG FcgammaR. In this study, we demonstrate that activation system, specifically generation C5a, initiates neutrophilic in IC peritonitis. We show ablation C5a receptor signaling abrogates neutrophil recruitment wild-type mice prevents enhancement migration seen FcgammaRIIB(-/-) mice, suggesting C5aR crucial initial event upstream FcgammaR...
Asthma is a major cause of morbidity worldwide with prevalence and severity still increasing at an alarming pace. Hallmarks this disease include early-phase bronchoconstriction subsequent eosinophil infiltration, symptoms that may be mimicked in vivo by the complement-derived C3a anaphylatoxin, following its interaction single-copy C3aR. We analyzed pathophysiological role anaphylatoxin model experimental OVA-induced allergic asthma, using inbred guinea pig strain phenotypically unresponsive...
The complement system is a major component of our innate immune system, in which the proteins C5a and C5a‐des Arg bind to two G‐protein‐coupled receptors: namely, receptor (C5a1) like‐2 (C5a2, formerly called C5L2). Recently, it has been demonstrated that C5a, but not Arg, upregulates heteromer formation between C5a1 C5a2, leading an increase IL‐10 release from human monocyte‐derived macrophages (HMDMs). A bioluminescence resonance energy transfer (BRET) assay was used assess recruitment...
Complement is a part of innate immunity that has critical role in the protection against microbial infections, bridges with adaptive and initiates inflammation. Activation complement, by specific recognition molecular patterns presented an activator, for example, pathogen cell, classical lectin pathways or spontaneously alternative pathway, leads to opsonization activator production pro-inflammatory molecules such as C3a anaphylatoxin. The biological function this anaphylatoxin regulated...
The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads profound activation complement system. Pathophysiological concepts suggest that occurs very early in this syndrome. Thus, we discuss whether determination concentrations components C3a, C5a, and C3 plasma as well C3a/C3 ratio might be helpful diagnose sepsis early. For purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels...
The anaphylatoxic peptide C3a is part of a basic immunological defense mechanism, the complement system. Research on human receptor and signal transduction hampered by lack suitable cell or line. We screened tumor lines blood cells for C3a-dependent increase in cytosolic Ca2+ ([Ca2+]i) analyzed this reaction fura-2/AM fluorescence assay suspension. U937 cells, when differentiated with dibutyryl-cAMP (Bt2cAMP), purified neutrophils reacted dose-dependent fashion to analogue synthetic peptide....
Abstract The PI3K/Akt signaling pathway has been recently suggested to have controversial functions in models of acute and chronic inflammation. Our group others reported previously that the complement split product C5a alters neutrophil innate immunity cell during onset sepsis is involved PI3K activation. We report this study vivo inhibition resulted increased mortality septic mice accompanied by strongly elevated serum levels TNF-α, IL-6, MCP-1, IL-10 as well decreased oxidative burst...
The intracellular bacterium Chlamydia trachomatis causes infections of urogenital tract, eyes or lungs. Alignment reveals homology CT166, a putative effector protein C. serovars, with the N-terminal glucosyltransferase domain clostridial glucosylating toxins (CGTs). CGTs contain an essential DXD-motif and mono-glucosylate GTP-binding proteins Rho/Ras families, master regulators actin cytoskeleton. CT166 is preformed in elementary bodies D detected host-cell shortly after infection. Infection...
Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention often sought too late, i.e., when the systemic inflammatory response already unleashed. This in turn limits success of antibiotic treatment. The complement system generally accepted as most important innate immune determinant against invasive meningococcal disease since it protects host through bactericidal membrane...