title: Prostaglandin E2 imprints a long-lasting effect on dendritic cell progenitors in the bone marrow.
abstract: Dendritic cells (DCs) that differentiate in vitro from the bone marrow (BM) of mice with prostaglandin E2 (PGE2)-associated inflammation of the skin, airways, or peritoneal cavity poorly initiate immune responses. To remove in vitro differentiation and allow BM-derived DCs to seed the periphery under steady-state conditions, as well as study the molecule proposed responsible, chimeric mice were engrafted for >16 wk with BM cells from mice exposed to PGE2. Serial PGE2-chimeric mice were established with BM cells from the primary chimeric mice. Immune responses in the airways and skin of the PGE2-chimeric mice and serial PGE2-chimeric mice were significantly attenuated. After inflammatory challenges by intranasal LPS, topical fluorescein isothiocyanate, and intraperitoneal alum, DCs, macrophages, and neutrophils trafficked poorly in PGE2-chimeric mice and serial PGE2-chimeric mice. Injection of BM-differentiated DCs from nonchimeric mice restored the reduced immune responses of PGE2-chimeric mice. DCs from BM of 16-wk-engrafted PGE2-chimeric and serial PGE2-chimeric mice resembled cells differentiated from BM exposed to PGE2 for only 3 d, demonstrating the long-lasting effect of PGE2 on DC progenitors. PGE2 attenuates systemic immune responses by modulating myeloid cell progenitors in the BM such that BM-derived, terminally differentiated myeloid cells have poor trafficking ability to sites of need.
authors: 1.University of Western Australia, 100 Roberts Road, Subiaco, WA 6008, Australia. prueh@ichr.uwa.edu.au.
authors: Naomi M
authors: NM
authors: Scott
authors: Royce L X
authors: RL
authors: Ng
authors: Shelley
authors: S
authors: Gorman
authors: Mary
authors: M
authors: Norval
authors: Jason
authors: J
authors: Waithman
authors: Prue H
authors: PH
authors: Hart
mesh_terms: D000281:Administration, Intranasal; D000287:Administration, Topical; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002678:Chimera / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D005720:Gamma Rays; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D007109:Immunity / Q000187:drug effects / Q000528:radiation effects; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008264:Macrophages / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D016650:Fluorescein-5-isothiocyanate; D015232:Dinoprostone
keywords: Immunosuppression; UV irradiation; chimeric mice; hemopoietic stem cells; inflammation; macrophages