A5079797111- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Mast cells and histamine
- Bone Metabolism and Diseases
- Angiogenesis and VEGF in Cancer
- Bone health and treatments
- Neonatal Respiratory Health Research
- Chemokine receptors and signaling
- ZnO doping and properties
- Congenital Diaphragmatic Hernia Studies
- IL-33, ST2, and ILC Pathways
- 3D Printing in Biomedical Research
- Protein Kinase Regulation and GTPase Signaling
- Tissue Engineering and Regenerative Medicine
- Cerebrospinal fluid and hydrocephalus
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Vascular Malformations and Hemangiomas
- Spinal Dysraphism and Malformations
- Sympathectomy and Hyperhidrosis Treatments
Semmelweis University
2014-2024
Science for Life Laboratory
2023
Uppsala University
2023
Hungarian Academy of Sciences
2014-2022
University of Pennsylvania
2012-2015
Cardiovascular Institute Hospital
2014
University of Freiburg
2013
University of California, San Francisco
2003
La Jolla Institute for Immunology
2003
To initiate adaptive immunity, dendritic cells (DCs) move from parenchymal tissues to lymphoid organs by migrating along stromal scaffolds that display the glycoprotein podoplanin (PDPN). PDPN is expressed lymphatic endothelial and fibroblastic reticular promotes blood-lymph separation during development activating C-type lectin receptor, CLEC-2, on platelets. Here, we describe a role for CLEC-2 in morphodynamic behavior motility of DCs. deficiency DCs impaired their entry into lymphatics...
The aim of the present study was to investigate role tyrosine phosphorylation pathways in fMLP-induced exocytosis different secretory compartments (primary and secondary granules, as well vesicles) neutrophils. Genistein, a broad specificity kinase inhibitor, blocked primary but had only marginal effect on release vesicles. Genistein also inhibited extracellular signal-regulated (ERK) p38 mitogen-activated protein kinases (MAPK), raising possibility that inhibition ERK and/or MAPK might be...
Mammals transport blood through a high-pressure, closed vascular network and lymph low-pressure, open network. These networks connect at the lymphovenous (LV) junction, where drains into an LV valve (LVV) prevents backflow of lymphatic vessels. Here we describe essential role for platelets in preventing from entering system junction. Loss CLEC2, receptor that activates response to endothelial cells, resulted backfilling with thoracic duct (TD) both neonatal mature mice. Fibrin-containing...
The β isoform of phosphoinositide 3-kinase may be an effective therapeutic target in inflammatory diseases.
Although Src family kinases participate in leukocyte function vitro, such as integrin signal transduction, their role inflammation vivo is poorly understood. We show that play a critical myeloid cell–mediated inflammatory reactions. Mice lacking the Hck, Fgr, and Lyn hematopoietic compartment were completely protected from autoantibody-induced arthritis skin blistering disease, well reverse passive Arthus reaction, with functional overlap between three kinases. Though overall phenotype...
The lung is a specialized barrier organ that must tightly regulate interstitial fluid clearance and prevent infection in order to maintain effective gas exchange. Lymphatic vessels are important for these functions other organs, but their roles the have not been fully defined. In present study, we addressed how lymphatic vasculature participates homeostasis. Studies using mice carrying reporter allele revealeded that, contrast collecting lack smooth muscle cells entirely, suggesting forward...
β2 integrins and Fcγ receptors are critically involved in neutrophil activation at the site of inflammation. Both receptor types trigger a receptor-proximal tyrosine phosphorylation cascade through Src family kinases Syk, but further downstream signaling events poorly understood. We show that phospholipase C (PLC) γ2 is phosphorylated Syk during integrin or Fc receptor-mediated neutrophils. PLCγ2−/− neutrophils completely defective functional responses such as respiratory burst,...
The Syk tyrosine kinase plays an important role in diverse functions hematopoietic lineage cells. Although previous vitro and pharmacologic analyses suggested to be a possible player the development of autoimmune arthritis, no vivo genetic studies addressing that issue have yet been reported. aim present study was test whether deficiency affects autoantibody-induced experimental arthritis K/BxN serum-transfer model.Syk(-/-) bone marrow chimeras carrying Syk-deficient system were generated by...
Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter mechanics in preparation for unknown. We identify prenatal lymphatic function as an unexpected requirement respiration. Mice lacking vessels, due either loss the lymphangiogenic factor CCBE1 or...
Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces function affected organs and results in degradation quality life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) stimulate lymphatic growth reduce experimental mouse models. We demonstrated administration a single low-dose VEGFC...
Molecular heterogeneity of endothelial cells underlies their highly specialized functions during changing physiological conditions within diverse vascular beds. For example, placental spiral arteries (SAs) undergo remarkable remodeling to meet the ever-growing demands fetus - a process which is deficient in preeclampsia. The extent maternal coordinate with immune and pregnancy hormones promote SA remains largely unknown. Here we found that remodeled SAs expressed lymphatic markers PROX1,...
Abstract Immune complex-induced activation of neutrophils through cell surface FcRs plays a central role in the pathogenesis autoimmune inflammatory diseases. These diseases are often modeled using genetically modified mice. However, contrast to number studies on human cells, identity involved immune complex murine is at present unknown. Furthermore, little known about cellular functions mediated by recently identified FcγRIV. In this study, we tested plate-bound complexes, various knockout...
Recently, the presence of lymphatic structures has been demonstrated in dura mater, which contrast to classical view indicating lack lymphatics central nervous system (CNS). Moreover, role meningeal pathogenesis Alzheimer's disease and multiple sclerosis was suggested. However, possible regulators developmental program function remain unclear. Here, we aimed at characterizing lymph flow dependence lymphatics. First, that present mater are involved uptake transport macromolecules from CNS....
The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role beta(2) integrin-mediated leukocyte activation. To elucidate signaling pathway downstream of during beta2 integrin (CD11/CD18)-mediated migration extravasation polymorphonuclear neutrophils (PMN), we generated neutrophil-like differentiated HL-60 (dHL-60) cells expressing a fluorescently tagged mutant lacking residue at position 323 (Syk-Tyr323) that known to be required for...
Eur J Clin Invest 2012; 42 (1): 49–60 Abstract Background Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule diverse haematopoietic lineages. Here, we tested the of PLCγ2 and ovariectomy‐induced resorption, as well vitro osteoclast cultures using PLCγ2‐deficient (PLCγ2 −/− ) mice. Materials methods The...
Syk is a nonreceptor tyrosine kinase critically involved in signaling by various immunoreceptors including B-cell-receptors and activating Fc-receptors. We have previously shown that also mediates immunoreceptor-like signals required for the vitro development function of osteoclasts. However, perinatal lethality Syk–/– mice precluded analysis role vivo bone metabolism. To overcome problem, we generated with osteoclast-specific (SykΔOC) or hematopoietic (SykΔHaemo) deficiency conditional...
Abstract The relative contribution of integrin and nonintegrin signals to neutrophil activation is incompletely understood. Immobilized anti-integrin Abs were previously shown induce robust neutrophils without any additional stimulus, suggesting that cross-linking integrins sufficient for full the cells. However, possible from other receptors has not been tested in this system. In study, we show responses requires costimulation through low-affinity FcγRs. Murine lacking FcR γ-chain or...