Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*  

作　　者：George P. Albaugh Sudhir K. Dutta Vasantha Iyengar Samina Shami Althaf Lohani Eduardo Sainz George Kessie Prasanna Nair Sara Lagerholm Alka Kamra J.-H. Joshua Chen Shilpa Kalavapudi Rakesh Vinayek Robert Shores Laila E. Phillips Ram Nair Padmanabhan P. Nair George P. Albaugh;Sudhir K. Dutta;Vasantha Iyengar;Samina Shami;Althaf Lohani;Eduardo Sainz;George Kessie;Prasanna Nair;Sara Lagerholm;Alka Kamra;J.-H. Joshua Chen;Shilpa Kalavapudi;Rakesh Vinayek;Robert Shores;Laila E. Phillips;Ram Nair;Padmanabhan P. Nair(Beltsville Human Nutrition Research Centre, Agricultural Research Service, Beltsville, MD, USA;Division of Gastroenterology, Sinai Hospital of Baltimore, Baltimore, MD, USA;Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA;NonInvasive Technologies LLC, Elkridge, MD, USA;Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA)

机构地区：[1]Beltsville Human Nutrition Research Centre, Agricultural Research Service, Beltsville, MD, USA [2]Division of Gastroenterology, Sinai Hospital of Baltimore, Baltimore, MD, USA [3]Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA [4]NonInvasive Technologies LLC, Elkridge, MD, USA [5]Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA

出　　处：《Open Journal of Preventive Medicine》2020年第6期126-150,共25页预防医学期刊（英文）

摘　　要：Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

关 键 词：Colon Epithelial Cells CXCR-4 IgA/IgG Chimeric Immunoglobulin Heterodimer COX-2 LGR-5 Musashi-1 Dedifferentiation Cellular Engraftment Oncoly-sis Gastrointestinal Progenitor Stem Cells (GIP-C) 

分 类 号：X70[环境科学与工程—环境工程]