- Immune Response and Inflammation
- Vasculitis and related conditions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Sarcoidosis and Beryllium Toxicity Research
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Fatty Acid Research and Health
- Cancer Research and Treatments
- Blood transfusion and management
- Blood disorders and treatments
- Blood groups and transfusion
- Inflammatory mediators and NSAID effects
- Lung Cancer Treatments and Mutations
- Clinical Nutrition and Gastroenterology
- NF-κB Signaling Pathways
- Biopolymer Synthesis and Applications
- Nephrotoxicity and Medicinal Plants
- Respiratory Support and Mechanisms
- Mast cells and histamine
- Microbial Inactivation Methods
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Lung Cancer Diagnosis and Treatment
German Center for Lung Research
2016-2023
Justus-Liebig-Universität Gießen
2001-2023
Universities of Giessen and Marburg Lung Center
2009-2023
Giessen School of Theology
1997-2009
University of Konstanz
2005-2009
German Red Cross
2005
Luther University
2005
Martin Luther University Halle-Wittenberg
2005
Charité - Universitätsmedizin Berlin
2003
Deutsche Forschungsgemeinschaft
2002
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Free oxygen radicals have been implicated in the pathogenesis of disorders. Therefore, we aimed to test hypothesis that oxidative stress constitutes one underlying mechanism for connection between OSA disease. In 18 patients release superoxide from polymorphonuclear neutrophils was determined after stimulation bacterial tripeptide formylmethionylleucylphenylalanine (fMLP) calcium ionophore A23....
Infusion of fish oil-based (n-3) lipids may influence leukocyte function and plasma in critical care patients. Twenty-one patients with sepsis requiring parenteral nutrition were randomized to receive an n-3 lipid emulsion rich eicosapentaenoic acid docosahexaenoic or a conventional (n-6) (index fatty acid: arachidonic acid) for 5 days. The impact on plasma-free acids, mononuclear cytokine generation, membrane composition was examined. Cytokine synthesis by isolated elicited endotoxin....
The inflammatory tumor microenvironment plays a crucial role in progression. In lung cancer, both bacterial infections and neutrophilia are associated with poor prognosis. this study, we characterized the effect of isolated human neutrophils on proliferation non-small cell cancer (NSCLC) line A549 analyzed impact A549-neutrophil interactions mediator generation naive lipopolysaccharide (LPS)-exposed cultures. Co-incubation cells induced resting LPS-exposed dose-dependent manner....
Lung cancer is frequently complicated by pulmonary infections which may impair prognosis of this disease. Therefore, we investigated the effect bacterial lipopolysaccharides (LPS) on tumor proliferation in vitro non-small cell lung (NSCLC) line A549, ex vivo a tissue culture model using human NSCLC specimens and A549 adenocarcinoma mouse model. LPS induced time- dose-dependent increase cells as quantified MTS activity counting. In parallel, an increased expression marker Ki-67 cyclooxygenase...
Pulmonary infections are frequent complications in lung cancer and may worsen its outcome survival. Inflammatory mediators suspected to promote tumor growth non-small-cell (NSCLC). Hence, bacterial pathogens affect by activation of inflammatory signalling. Against this background, we investigated the effect purified lipoteichoic acids (LTA) Staphylococcus aureus (S. aureus) on cellular proliferation liberation interleukin (IL)-8 NSCLC cell lines A549 H226. as well H226 cells constitutively...
Among the anti-neutrophil cytoplasmic antibodies (ANCA), those targeting proteinase 3 (PR3) have a high specificity for Wegener's granulomatosis (WG). It is known that preceding priming of neutrophils with cytokines prerequisite membrane surface expression PR3, which then accessible to autoantibody binding. Employing monoclonal antibody directed against human PR3 and ANCA-positive serum from WG patients we now investigated role free arachidonic acid (AA) in autoantibody-related neutrophil...
Anti–neutrophil cytoplasmic antibodies (ANCAs) targeting proteinase 3 (PR3) have a high specifity for Wegener's granulomatosis (WG), and their role in activating leukocytes is well appreciated. In this study, we investigated the influence of PR3-ANCA murine monoclonal on human umbilical vascular endothelial cells (HUVECs). Priming HUVECs with tumor necrosis factor α induced upregulation PR3 message surface expression antigen, as measured by Cyto-ELISA, maximum occurrence after 2 h. Primed...
ABSTRACT Polymorphonuclear leukocytes (PMN) are essential for resolution of infections with Listeria monocytogenes . The present study investigated the role listerial exotoxins listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PlcA) in human neutrophil activation. Different strains, mutated individual virulence genes, as well purified LLO were used. Coincubation neutrophils wild-type L. provoked PMN activation, occurring independently phagocytosis events, concomitant...
Objective: In sepsis, Gram-positive and Gram-negative bacteria provoke similar inflammatory processes. Whereas lipopolysaccharides (LPSs) are acknowledged as the principal immunostimulatory components of bacteria, effect cell wall component lipoteichoic acid (LTA) is less well characterized. present study, we investigated highly purified LTA from Staphylococcus aureus on cytokine generation by isolated human neutrophils. Subjects: Isolated neutrophils healthy volunteers. Interventions:...
Summary Polymorphonuclear neutrophils (PMN) have been implicated in various vascular inflammatory processes. We isolated PMN from venous blood samples of 10 patients with severe primary pulmonary arterial hypertension (PPH), 7 secondary to chronic thromboembolism (CTEPH), and 12 healthy controls. When stimulated the calcium-ionophore A23187, platelet activating factor (PAF) or microbial agent n-formyl-Methionyl-Leucyl-Phenylalanine (fMLP), significantly increased release elastase super-oxide...
Abstract Antineutrophil cytoplasmic antibodies (ANCA) targeting proteinase 3 [PR3; ANCA (c-ANCA)], a leukocyte serine protease, are highly specific for Wegener's Granulomatosis (WG). A pathogenetic role c-ANCA has been proposed as result of their ability activating neutrophils, whereas interaction with monocytes is less well characterized. We investigated the influence monoclonal anti-PR3 (anti-PR3) and from WG sera on monocyte cytokine prostanoid release. found that PR3 was expressed...
Anti-neutrophil cytoplasmic antibodies (c-ANCA) targeting proteinase 3 (PR3) are implicated in the pathogenesis of Wegener's granulomatosis (WG). Fulminant disease can present as acute lung injury (ALI). In this study, a model ALI WG was developed using isolated rat lungs. Isolated human polymorphonuclear leukocytes (PMNs) were primed with tumour necrosis factor (TNF) to induce surface expression PR3. Co-perfusion TNF-primed neutrophils and monoclonal anti-PR3 induced massive weight gain...
Although cytokine synthesis in polymorphonuclear leukocytes (PMN) was shown to be modulated by soluble mediators, the impact of microenvironmental conditions has not been elucidated. In this study, we investigated effect cell density on release from human neutrophils. PMN were cultured at various densities (10 x 10(6) PMN/ml; 60 PMN/ml), and LPS-induced cytokines quantified ELISA technique. Upon an increase density, secretion CXC chemokine IL-8 progressively reduced. This paralleled a...
Abstract In Wegener's granulomatosis (WG), a pathogenetic role has been proposed for circulating anti-neutrophil-cytoplasmic antibodies (ANCA) targeting proteinase 3 (PR3). Disease activation in WG appears to be triggered by bacterial infections. the present study, we characterized effect of anti-PR3 on vitro isolated monocytes and neutrophils cell-wall components lipopolysaccharide (LPS) lipoteichoic acid (LTA). Although sole incubation with monoclonal induced release minor quantities...
Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis.In the present study we perfused isolated rat hearts for 180 minutes with highly purified LTA from Staphylococcus aureus. A progressive decline of left ventricular contractile function paralleled by expression myocardial tumor necrosis factor-alpha (TNF-alpha) mRNA and protein as well release TNF-alpha into perfusate was observed LTA-perfused hearts. Employment an anti-TNF-alpha antibody completely prevented...
Abstract Proinflammatory cytokines are centrally involved in tumor progression and survival non–small cell lung cancer, both the presence of infiltrating neutrophils bacterial infection may indicate a poor prognosis. Against this background, we investigated effect wall component lipopolysaccharide (LPS) on interleukin (IL)-6 IL-8 synthesis cancer line A549 A549-neutrophil cocultures. The LPS induced dose-dependent time-dependent release from cells, whereas IL-6 could not be detected....
Objective: In sepsis, cardiac function is frequently depressed. Microcirculatory disturbances as evidenced in most organs may extend to the coronary circulation and play a role occurrence of dysfunction. Staphylococcal α-toxin Escherichia coli hemolysin (ECH), pore-forming exotoxins clinically relevant bacteria, have recently been demonstrated evoke dysfunction isolated rat hearts by activating myocardial eicosanoid metabolism. α-Toxin activates synthesis thromboxane (Tx) A2, ECH...
Abstract Anti-neutrophil cytoplasmic antibodies (ANCA) targeting proteinase 3 (PR3) possess a high sensitivity and specificity for Wegener's granulomatosis. Due to their capacity of directly activating neutrophils, pathogenetic role these autoantibodies has been proposed. We investigated the impact subthreshold concentrations monoclonal anti-PR3 (anti-PR3; 0.1 μg/mL) on neutrophil activation elicited by secondary agent. Preincubation with resulted in massive amplification...
Objective Exposure of neutrophils to low doses bacterial lipopolysaccharides enhances their readiness respond with inflammatory mediator generation including oxygen radical formation a subsequently applied stimulus (“priming”). In the present study, we investigated role lipid synthesis and impact anti-inflammatory cytokine interleukin-10 on lipopolysaccharide-dependent priming human in response N-formyl-methionyl-leucyl-phenylalanine. Design Prospective, experimental study. Setting Research...
Non-small cell lung cancer (NSCLC) has a very poor prognosis even when treated with the best therapies available today often including radiation. NSCLC is frequently complicated by pulmonary infections which appear to impair as well therapy, whereby underlying mechanisms are still not known. It was investigated here, whether bacterial lipopolysaccharides (LPS) might alter tumor radiosensitivity. LPS were found induce radioresistance but solely in cells an active TLR-4 pathway. Proteome...
Abstract Among the anti-neutrophil cytoplasmic Abs (ANCA), those targeting proteinase 3 (PR3) have a high sensitivity and specificity for Wegener’s granulomatosis (WG). A pathogenetic role these autoantibodies has been proposed due to their capacity of activating neutrophils in vitro. Recently, PR3 was also detected human renal tubular epithelial cells (TEC). In present study, effect murine monoclonal anti-PR3 (anti-PR3) purified c-ANCA from WG serum on isolated cell signaling inflammatory...