A5028973880- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pneumonia and Respiratory Infections
- Immune cells in cancer
- Respiratory viral infections research
- Pulmonary Hypertension Research and Treatments
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Respiratory Support and Mechanisms
- Protease and Inhibitor Mechanisms
- Asthma and respiratory diseases
- Cardiac Ischemia and Reperfusion
- Mechanical Circulatory Support Devices
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Tuberculosis Research and Epidemiology
- Influenza Virus Research Studies
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Bacterial Infections and Vaccines
- Pleural and Pulmonary Diseases
- Cardiac and Coronary Surgery Techniques
- Immune responses and vaccinations
Medizinische Hochschule Hannover
2015-2024
German Center for Lung Research
2015-2024
Clinica de Pneumologie Iaşi
2010-2021
McMaster University
2020
German Center for Infection Research
2014-2017
Jena University Hospital
2012
Fraunhofer Institute for Toxicology and Experimental Medicine
2008
Orthopädische Universitätsklinik
2007
RWTH Aachen University
2007
Justus-Liebig-Universität Gießen
1997-2006
Abstract Influenza A virus pneumonia is characterized by severe lung injury and high mortality. Early infection elicits a strong recruitment of monocytes from the peripheral blood across endo-/epithelial barrier into alveolar air space. However, it currently unclear which infected resident cell populations, epithelial cells or macrophages, elicit monocyte during influenza infection. In current study, we investigated whether primary macrophages would basal-to-apical transepithelial migration...
Coordinated neutrophil and monocyte recruitment is a characteristic feature of acute lung inflammatory responses. We investigated the role chemotactic protein-1 (CCL2, JE) chemokine receptor CCR2 in regulating alveolar leukocyte traffic. Groups wild-type (WT) mice, CCR2-deficient lethally irradiated WT mice that were reciprocally bone marrow transplanted (chimeric deficient WT, respectively), chimeric with an enriched CCR2(+) macrophage population, transfused mononuclear cells treated...
The CC chemokine ligand 2 (CCL2) (JE, monocyte chemotactic protein-1 [MCP-1]) and its receptor (CCR2) are critical regulators of monocyte/macrophage trafficking. Recently, we demonstrated that application exogenous CCL2 in the lungs mice induced accumulation airspace, whereas combined bronchoalveolar instillation Escherichia coli endotoxin provoked both enhanced extensive neutrophil influx associated with loss pulmonary endothelial/epithelial barrier function. In this study, investigated...
Abstract Potential impact of ω-3 fatty acids, as contained in fish oil, on immunological function has been suggested because observations reduced inflammatory diseases Greenland Inuit were published. A oil-based lipid emulsion recently approved for parenteral nutrition many countries. We investigated the influence a short infusion course (ω-3) vs conventional (ω-6) monocyte function. In randomized design, twelve healthy volunteers received or ω-6 48 h, with cross-over repetition after 3 mo....
In the acute respiratory distress syndrome, recruitment of peripheral blood monocytes results in expansion total pool resident alveolar macrophages. The fate macrophages, or whether recruited are selectively eliminated from airspace differentiate into macrophages during resolving phase inflammation, has not been determined. Here, we analyzed kinetics and macrophage turnover within untreated LPS-challenged mice. Using bone marrow chimeric CD45.2 mice that were generated by lethal irradiation...
Experimental models are critical for the understanding of lung health and disease indispensable drug development. However, pathogenetic clinical relevance is often unclear. Further, use animals in biomedical research controversial from an ethical perspective. The objective this task force was to issue a statement with recommendations about by facilitating in-depth discussions between respiratory scientists, provide overview literature on available models. Focus put their specific benefits...
Idiopathic pulmonary fibrosis (IPF) is a diffuse parenchymal lung disease characterized by exuberant deposition of extracellular matrix (ECM) proteins in the interstitium, which contributes to substantial morbidity and mortality IPF patients. Matrix metalloproteinases (MMPs) are large family zinc-dependent endopeptidases, many have been implicated regulation ECM degradation fibrosis. However, roles MMP-2 -9 (also termed gelatinases A B) not yet explored detail.AdTGF-β1 was applied via...
In 49 acute respiratory distress syndrome (ARDS) patients, the phenotype of alveolar macrophages (AMs) was analyzed by flow cytometry. Bronchoalveolar lavage (BAL) performed within 24 h after intubation and on days 3– 5, 9– 12, 18– 21 mechanical ventilation. The 27E10 high /CD11b /CD71 low / 25F9 /HLA DR /RM3/1 AM population in first BAL indicated extensive monocyte influx into compartment. There no evidence increased local proliferation as assessed nuclear Ki67 staining. Sequential revealed...
The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident macrophages (rAMs). Using intravenous injected fluorescent dye PKH26, which accumulated rAMs without labeling blood leukocytes, we developed a technique that permits identification, isolation, functional analysis lung alveoli mice. Alveolar deposition murine JE, homologue human monocyte chemoattractant...
Abstract Mononuclear phagocytes are critical components of the innate host defense lung to inhaled bacterial pathogens. The monocyte chemotactic protein CCL2 plays a pivotal role in inflammatory mononuclear phagocyte recruitment. In this study, we tested hypothesis that increased CCL2-dependent recruitment would improve infection with Streptococcus pneumoniae. transgenic mice overexpress human type II alveolar epithelial cells and secrete it into air space showed similar proinflammatory...
Neutrophil serine proteases cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3) have recently been shown to contribute killing of Streptococcus pneumoniae in vitro. However, their relevance lung-protective immunity against different serotypes S. vivo has not determined so far. Here, we examined the effect CG CG/NE deficiency on lung host defense mice. Despite similar recruitment, both knockout (KO) mice double-KO infected with focal pneumonia-inducing serotype 19 demonstrated...
Sustained neutrophilic infiltration is known to contribute organ damage, such as acute lung injury. CXC chemokine receptor 2 (CXCR2) the major regulating inflammatory neutrophil recruitment in and chronic inflamed tissues. Whether or not abundant observed severe pneumonia essential for protective immunity against Streptococcus pneumoniae infections incompletely defined. Here we show that CXCR2 deficiency severely perturbs of both neutrophils exudate macrophages associated with a massive...
Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming inflammation in response bacterial challenge. However, the underlying apoptotic mechanism has not been defined. Here, we examined role TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) S. pneumoniae–induced macrophage apoptosis, and investigated potential benefit TRAIL-based therapy pneumococcal pneumonia mice. Compared WT mice, Trail−/−...
The growth factor GM-CSF has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities lung sentinel cells. However, potential intra-alveolar to augment protective immunity against inhaled bacterial pathogens not been defined preclinical infection models. We hypothesized that transient overexpression lungs mice by adenoviral gene transfer (Ad-GM-CSF) would protect from subsequent lethal pneumococcal pneumonia. Our data show delivery Ad-GM-CSF led...
The role of macrophage-inducible C-type lectin Mincle in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed induction on resident alveolar macrophages and newly immigrating exudate to Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14-21 posttreatment. As compared WT mice, knockout (KO) exhibited decreased proinflammatory mediator responses leukocyte recruitment upon M. BCG...
Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced alveolar macrophages and neutrophils bronchoalveolar lavage fluids mice patients with pneumococcal pneumonia. Moreover, S. directly triggered reporter cell activation vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which identified as ligand...
Intratracheal instillation of the monocyte chemoattractant JE/monocyte protein (MCP)-1 in mice was recently shown to cause increased alveolar accumulation absence lung inflammation, whereas combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute inflammation with early neutrophil and delayed influx. We evaluated role resident macrophages (rAM) these leukocyte recruitment events related phenomena inflammation. Depletion rAM by pretreatment liposomal clodronate did not affect...
Abstract Alveolar monocyte influx requires adherence and transmigration through the vascular endothelium, extracellular matrix, alveolar epithelium. For investigating migratory process across epithelial barrier, we employed both A549 cell line isolated human cells. Under baseline conditions, spontaneous bidirectional transepithelial migration was noted, which dose-dependently increased in presence of chemoattractant protein-1. TNF-α stimulation epithelium provoked polarized apical secretion...
Abstract The monocyte chemoattractant CCL2 is of major importance in inflammatory recruitment to the lungs response bacterial infection. Streptococcus pneumoniae most prevalent pathogen community-acquired pneumonia causing significant morbidity and mortality worldwide. In current study, we examined role lung-protective immunity against two strains S. exhibiting different virulence profiles. Both wild-type mice knockout (KO) became septic within 24 h infection with serotype 3 died by day 4...
Abstract The neutrophil serine proteases cathepsin G (CG) and elastase (NE) are involved in immune-regulatory processes exert antibacterial activity against various pathogens. To date, their role therapeutic potential pulmonary host defense mycobacterial infections poorly defined. In this work, we studied the roles of CG NE resistance Mycobacterium bovis bacillus Calmette-Guérin (BCG). CG-deficient mice even more pronounced CG/NE-deficient showed significantly impaired pathogen elimination...