Sandra Beer-hammer - Academia.edu (original) (raw)

Papers by Sandra Beer-hammer

International Journal of Molecular Sciences, Dec 24, 2023

Journal of Immunology, 2013

Heterotrimeric G proteins of the Ga i family have been implicated in signaling pathways regulatin... more Heterotrimeric G proteins of the Ga i family have been implicated in signaling pathways regulating cell migration in immune diseases. The Ga i-protein-coupled C5a receptor is a critical regulator of IgG FcR function in experimental models of immune complex (IC)-induced inflammation. By using mice deficient for Ga i2 or Ga i3 , we show that Ga i2 is necessary for neutrophil influx in skin and lung Arthus reactions and agonist-induced neutrophilia in the peritoneum, whereas Ga i3 plays a less critical but variable role. Detailed analyses of the pulmonary IC-induced inflammatory response revealed several shared functions of Ga i2 and Ga i3 , including mediating C5a anaphylatoxin receptor-induced activation of macrophages, involvement in alveolar production of chemokines, transition of neutrophils from bone marrow into blood, and modulation of CD11b and CD62L expression that account for neutrophil adhesion to endothelial cells. Interestingly, C5a-stimulated endothelial polymorphonuclear neutrophil transmigration, but not chemotaxis, is enhanced versus reduced in the absence of neutrophil Ga i3 or Ga i2 , respectively, and knockdown of endothelial Ga i2 caused decreased transmigration of wild-type neutrophils. These data demonstrate that Ga i2 and Ga i3 contribute to inflammation by redundant, overlapping, and Ga i-isoform-specific mechanisms, with Ga i2 exhibiting unique functions in both neutrophils and endothelial cells that appear essential for polymorphonuclear neutrophil recruitment in IC disease.

European Respiratory Journal, Sep 1, 2014

Background: The predominantly haematopoeticaly expressed class I PI3-kinases γ and δ have been sh... more Background: The predominantly haematopoeticaly expressed class I PI3-kinases γ and δ have been shown to be important in the development of asthma bronchiale. So far, it is not clear which specific roles these two PI3Ks play in asthma. Aim: To determine the biological function of PI3Kγ and PI3Kδ in asthma. Methods: We examined C57BL/6N mice deficient for the catalytic subunit of PI3Kγ and δ, i.e. p110γ and p110δ, together with their WT littermates in an experimental ovalbumin-induced asthma model. Severity of asthma was analysed by measuring lung functions using the isolated perfused mouse lung. Cellular changes were analysed by collecting BAL fluid (BALf) and lung tissue by flow cytometry. Results: Ovalbumin-induced asthma resulted in a significant increase in AHR upon methacholine challenge in WT mice and a significant inflammation in WT lungs. Interestingly, measurement of AHR in both KO mouse models revealed no reduction. However, analysis of BALf showed a significant reduction of eosinophils, neutrophils and T cells in p110γ and p110δ KO mice. Analysis of lung tissue of asthmatic mice revealed elevated cell counts in p110γ KO lungs only. In p110γ KO mice levels of neutrophils were significantly increased in comparison to WT, whereas in p110δ KO neutrophils and eosinophils were significantly reduced. IgE levels were elevated in asthmatic p110γ KO mice. Conclusion: Despite our observation, that deficiency for p110γ or p110δ in asthmatic mice produces different inflammatory patterns the AHR is not reduced in both models. Reduced cell counts in BALf of p110γ KO mice seemed to be caused by an interference with diapedesis, whereas reduced cell counts in p110δ KO mice may be caused by a reduced differentiation of inflammatory cells in our model.

Data in Brief, Feb 1, 2023

Frontiers in Molecular Biosciences, Oct 14, 2022

(2022), Untargeted stable isotoperesolved metabolomics to assess the effect of PI3Kβ inhibition o... more (2022), Untargeted stable isotoperesolved metabolomics to assess the effect of PI3Kβ inhibition on metabolic pathway activities in a PTEN null breast cancer cell line.

European Journal of Immunology, Nov 13, 2014

The adaptor protein SLy2 (Src homology domain 3 lymphocyte protein 2) is located on human chromos... more The adaptor protein SLy2 (Src homology domain 3 lymphocyte protein 2) is located on human chromosome 21 and was reported to be among a group of genes amplified in Down's syndrome (DS) patients. DS patients characteristically show an impaired immunity to pneumococcal infections. However, molecular mechanisms linking gene amplifications with specific DS phenotypes remain elusive. To investigate the effect of SLy2 gene amplification on the mammalian immune system, we studied SLy2 overexpressing transgenic-SLy2 (TG) mice. We found that baseline immunoglobulin M (IgM) levels as well as IgM responses following Pneumovax immunizations were reduced in TG mice. Moreover, B-1 cells, the major natural IgM-producing population in mice, were reduced in the peritoneal cavity of TG mice, while other immune cell compartments were unaltered. Mechanistically, SLy2 overexpression attenuated the expression of the IL-5 receptor α chain on B-1 cells, resulting in decreased B-1 cell numbers and decreased differentiation into Ab-secreting cells. Since B-1 cells essentially contribute to immunity against Streptococcus pneumoniae, the present study provides a novel molecular link between SLy2 expression and pneumococcal-specific IgM responses in vivo. These studies suggest that the adaptor protein SLy2 is a potential future target for immunomodulatory strategies for pneumococcal infections.

GTH Congress 2023 – 67th Annual Meeting of the Society of Thrombosis and Haemostasis Research – The patient as a benchmark

Molecular Imaging and Biology

Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for is... more Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (GiPCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of GiPCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of GiPCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain...

Frontiers in Neuroscience

Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating la... more Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating large-scale brain function given behavioral tasks. Previous studies have either applied sedatives during scanning or pre-treatment of anesthetics, e.g., isoflurane, to reduce the motion of animals, which could confound the brain function of “awake” states in rodents. Here, we have established a long training awake mouse fMRI-pupillometry paradigm/setup without the initial use of anesthesia. To validate the awake mouse fMRI platform, evoked BOLD-fMRI was performed to identify brain activation in the visual cortex, dorsal lateral geniculate nuclei, and superior colliculus. Furthermore, pupil signal fluctuation was investigated during scanning, showing a less dilated pupil after 5–8 weeks of intermittent training. Thus, using the awake mouse fMRI with real-time pupillometry provides a longitudinal functional mapping tool to study fully conscious mice.

To determine the number of eosinophils, neutrophils, T and B cells in the BALF from OVA-... more To determine the number of eosinophils, neutrophils, T and B cells in the BALF from OVA-treated and PBS-treated KO and corresponding WT mice, cells were collected, and analysed by flow cytometry. Cell counts were normalised as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159310#pone.0159310.g002" target="_blank">Fig 2</a>. (A) Eosinophils (eos) in BALF from p110γ-/- and WT mice (left), from p110δ-/- and WT mice (middle), and from p110γ/δ-/- and WT mice (right). (B) Neutrophils (neutros) in BALF from p110γ-/- and WT mice (left), p110δ-/- and WT mice (middle), and p110γ/δ-/- and WT mice (right). (C) T cells in BALF from p110γ-/- and WT mice (left), p110δ-/- and WT mice (middle), and p110γ/δ-/- and WT mice (right). (D) B cells in BALF from p110γ-/- and WT mice (left), p110δ-/- and WT mice (middle), and p110γ/δ-/- and WT mice (right). Data (n = 3–6) are presented as means + SD. Data were analysed by One-way ANOVA followed by Bonferroni’s comparison tests for selected pairs of columns. +++ P < 0.001, ++ P < 0.01, + P < 0.05. + indicate differences between WT PBS and WT OVA groups. ***P < 0.001, **P < 0.01, *P < 0.05. Asterisks indicate differences between OVA-treated groups.</p

Expression of CXCR4 and CXCL12/SFD-1α in WT, p110γ−/−, p110δ−/−, and p110γ/δ−/− mice. a To measur... more Expression of CXCR4 and CXCL12/SFD-1α in WT, p110γ−/−, p110δ−/−, and p110γ/δ−/− mice. a To measure CXCL12/SDF-1α concentrations in the BM, tibias were flushed with 500 μl PBS, cells were pelleted and supernatants were subsequently subjected to ELISA. Bars represent means + SD of n = 9–10 mice per group. b To determine CXCR4 expression leukocyte suspensions were labeled with fluorescent antibodies and analyzed by flow cytometry. Neutrophils were gated as singlet, live CD3ε − CD19− CD11b+ Siglec-F− Ly6G+ cells and were analyzed for the expression of CXCR4 (CD184). Shown are GMFI of CD184-APC of gated neutrophils in BM (left), blood (middle) and spleen (right). Bars represent means + SD of n = 5–8 mice per group. c To determine CXCR2 expression leukocyte suspensions were labeled with fluorescent antibodies and analyzed by flow cytometry. Neutrophils were gated as singlet, live CD3ε − CD19− CD11b+ Siglec-F− Ly6G+ cells and were analyzed for the expression of CXCR2 (CD182). Shown are GMF...

Encyclopedia of Molecular Pharmacology, 2021

Immunity, Inflammation and Disease, 2020

BackgroundDespite the benefits of existing vaccines, Streptococcus pneumoniae is still responsibl... more BackgroundDespite the benefits of existing vaccines, Streptococcus pneumoniae is still responsible for the greatest proportion of respiratory tract infections around the globe, thereby substantially contributing to morbidity and mortality in humans. B‐1 cells are key players of bacterial clearance during pneumococcal infection and even provide long‐lasting immunity towards S. pneumoniae. Previous reports strongly suggest an essential role of the immunoinhibitory adapter Src homology domain 3 lymphocyte protein 2 (SLy2) for B‐1 cell‐mediated antibody production. The objective of this study is to evaluate S. pneumoniae‐directed B cell responses in the context of SLy2 deficiency.MethodsB‐1 cell populations were analyzed via flow cytometry before and after pneumococcal immunization of SLy2‐deficient and wild‐type control mice. Global and vaccine‐specific immunoglobulin M (IgM) and IgG antibody titers were assessed by enzyme‐linked immunosorbent assay. To investigate survival rates durin...

Journal of Immunology, 2012

Journal of Molecular Medicine, 2019