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Start Over Author "Yaron Vagima" Publisher american society for clinical investigation
2 results on '"Yaron Vagima"'

1. Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2

Author

Reut Falach, Liat Bar-On, Shlomi Lazar, Tamar Kadar, Ohad Mazor, Moshe Aftalion, David Gur, Yentl Evgy, Ohad Shifman, Tamar Aminov, Ofir Israeli, Inbar Cohen-Gihon, Galia Zaide, Hila Gutman, Yaron Vagima, Efi Makdasi, Dana Stein, Ronit Rosenfeld, Ron Alcalay, Eran Zahavy, Haim Levy, Itai Glinert, Amir Ben-Shmuel, Tomer Israely, Sharon Melamed, Boaz Politi, Hagit Achdout, Shmuel Yitzhaki, Chanoch Kronman, and Tamar Sabo

Subjects
COVID-19, Medicine
Abstract

Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2–refractive CD-1 mice susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low doses of the acute lung injury stimulants bleomycin or ricin caused severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates greater than 50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart, and serum of low-dose ricin–pretreated mice compared with non-pretreated mice. Furthermore, lung extracts prepared 2–3 days after viral infection contained subgenomic mRNA and virus particles capable of replication only when derived from the pretreated mice. The deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against the SARS-CoV-2 receptor binding domain (RBD). Thus, viral cell entry in the sensitized mice seems to depend on viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. This unique mode of viral entry, observed over a mildly injured tissue background, may contribute to the exacerbation of coronavirus disease 2019 (COVID-19) pathologies in patients with preexisting morbidities.

Published
2021
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2. MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization

Author

Ester Rosenthal, Tsvee Lapidot, Shoham Shivtiel, Karin Golan, Orit Kollet, Abraham Avigdor, Polina Goichberg, David Naor, Arnon Nagler, Isabelle Petit, Alexander Kalinkovich, Ayelet Dar, Igor B. Resnick, Orly Perl, Melania Tesio, Yaron Vagima, Yechiel N. Gellman, and Izhar Hardan

Subjects
CD34, Antigens, CD34, Bone Marrow Cells, Mice, SCID, GPI-Linked Proteins, Gene Expression Regulation, Enzymologic, Mice, Antigens, CD, Cell Movement, Mice, Inbred NOD, Granulocyte Colony-Stimulating Factor, Matrix Metalloproteinase 14, Animals, Humans, RNA, Messenger, Progenitor cell, RNA, Small Interfering, Cell adhesion, Hematopoietic Stem Cell Mobilization, Mice, Knockout, Membrane Glycoproteins, biology, Chimera, Chemotaxis, CD44, General Medicine, Hematopoietic Stem Cells, Molecular biology, Cell biology, Gene Expression Regulation, Neoplastic, Haematopoiesis, biology.protein, Homing (hematopoietic), Research Article
Abstract

The mechanisms governing hematopoietic progenitor cell mobilization are not fully understood. We report higher membrane type 1–MMP (MT1-MMP) and lower expression of the MT1-MMP inhibitor, reversion-inducing cysteine-rich protein with Kazal motifs (RECK), on isolated circulating human CD34+ progenitor cells compared with immature BM cells. The expression of MT1-MMP correlated with clinical mobilization of CD34+ cells in healthy donors and patients with lymphoid malignancies. Treatment with G-CSF further increased MT1-MMP and decreased RECK expression in human and murine hematopoietic cells in a PI3K/Akt-dependent manner, resulting in elevated MT1-MMP activity. Blocking MT1-MMP function by Abs or siRNAs impaired chemotaxis and homing of G-CSF–mobilized human CD34+ progenitors. The mobilization of immature and maturing human progenitors in chimeric NOD/SCID mice by G-CSF was inhibited by anti–MT1-MMP treatment, while RECK neutralization promoted motility and egress of BM CD34+ cells. BM c-kit+ cells from MT1-MMP–deficient mice also exhibited inferior chemotaxis, reduced homing and engraftment capacities, and impaired G-CSF–induced mobilization in murine chimeras. Membranal CD44 cleavage by MT1-MMP was enhanced following G-CSF treatment, reducing CD34+ cell adhesion. Accordingly, CD44-deficient mice had a higher frequency of circulating progenitors. Our results reveal that the motility, adhesion, homing, and mobilization of human hematopoietic progenitor cells are regulated in a cell-autonomous manner by dynamic and opposite changes in MT1-MMP and RECK expression.

Published
2009

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