Antibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil recruitment in mice, thereby reducing antibacterial host defense, inflammatory disease, and hematopoietic stem cell mobilization. Here, we investigated the working mechanism of the CD97 antibody 1B2. Applying sterile models of inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the complement component C3, or the FcR common γ-chain, we show that 1B2 acts in vivo independent of ligand-binding interference by depleting PMN granulocytes in bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not complement activation and was associated with increased serum levels of TNF and other proinflammatory cytokines. Notably, depletion of granulocytes by CD97 antibody required acute inflammation, suggesting a mechanism of conditional, antibody-mediated granulocytopenia.
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http://dx.doi.org/10.1189/jlb.0510280 | DOI Listing |
Cell Rep Med
December 2024
The Zhongzhou Laboratory for Integrative Biology, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China. Electronic address:
Glioblastoma (GBM) stem cells (GSCs) contribute to poor prognosis in patients with GBM. Identifying molecular markers is crucial for developing targeted therapies. Here, we identify cluster of differentiation 97 (CD97) as an optimal GSC surface antigen for potential targeting by chimeric antigen receptor (CAR) T cell therapy through in vitro antibody screening.
View Article and Find Full Text PDFCell Rep
May 2024
Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA; Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address:
GPR133 (ADGRD1) is an adhesion G-protein-coupled receptor that signals through Gαs/cyclic AMP (cAMP) and is required for the growth of glioblastoma (GBM), an aggressive brain malignancy. The regulation of GPR133 signaling is incompletely understood. Here, we use proximity biotinylation proteomics to identify ESYT1, a Ca-dependent mediator of endoplasmic reticulum-plasma membrane bridge formation, as an intracellular interactor of GPR133.
View Article and Find Full Text PDFClin Proteomics
December 2023
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Background: Cell surface proteins perform critical functions related to immune response, signal transduction, cell-cell interactions, and cell migration. Expression of specific cell surface proteins can determine cell-type identity, and can be altered in diseases including infections, cancer and genetic disorders. Identification of the cell surface proteome remains a challenge despite several enrichment methods exploiting their biochemical and biophysical properties.
View Article and Find Full Text PDFNat Immunol
January 2024
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow.
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November 2023
Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA; Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address:
Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their potential as treatment targets. Here, we show that CD97 (ADGRE5) is the most promising aGPCR target in GBM, by virtue of its de novo expression compared to healthy brain tissue.
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