title: Irradiation enhances the support of haemopoietic cell transmigration, proliferation and differentiation by endothelial cells.
abstract: Endothelial cells (ECs) are a critical component of the bone marrow stroma in the regulation of haemopoiesis. Recovery of bone marrow aplasia after radiation exposure depends, in part, on the repair of radiation-induced endothelial damage. Therefore, we assessed the ability of an irradiated human bone marrow EC line (TrHBMEC) to support transmigration, proliferation and differentiation of CD34+ bone marrow cells either irradiated or not in transendothelial migration or co-culture models. Radiation-induced EC damage was reflected by an increased release of soluble intercellular adhesion molecule (sICAM)-1 and platelet endothelial cell adhesion molecule (PECAM)-1. Irradiation of TrHBMECs with a 10 Gy dose strongly enhanced the transmigration of CD34+ cells, granulo-monocytic progenitors (CFU-GM) and erythroid progenitors (BFU-E). While ICAM-1 and PECAM-1 expression on irradiated TrHBMECs was increased, only antibodies against PECAM-1 inhibited the radiation-induced enhanced transmigration of haemopoietic cells. Irradiation of TrHBMECs (5-15 Gy) also increased proliferation and differentiation towards the granulo-monocytic lineage of co-cultured CD34+ cells, as well as colony formation by those cells and the production of interleukin 6 (IL-6), IL-8, granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF. Irradiated TrHBMECs were more capable of stimulating irradiated (1,2 Gy) CD34+ cells and haemopoietic progenitors than non-irradiated TrHBMECs. Together, these results suggest that, despite the radiation-induced damage, irradiated ECs may favour haemopoietic reconstitution after radiation exposure.
authors.affiliation: Institut de Protection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, IPSN, Fontenay-aux-Roses, France. marie-helene.gaugler@ipsn.fr
authors.forename: M H
authors.initials: MH
authors.lastname: Gaugler
authors.forename: C
authors.initials: C
authors.lastname: Squiban
authors.forename: M A
authors.initials: MA
authors.lastname: Mouthon
authors.forename: P
authors.initials: P
authors.lastname: Gourmelon
authors.forename: A
authors.initials: A
authors.lastname: van der Meeren
mesh_terms: D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000528:radiation effects*; D018826:CD13 Antigens; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D002465:Cell Movement; D018920:Coculture Techniques; D004727:Endothelium / Q000166:cytology / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006098:Granulocytes; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016177:Macrophage-1 Antigen; D008858:Microscopy, Phase-Contrast; D009000:Monocytes; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D015850:Interleukin-6; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018826:CD13 Antigens