title: Impairment of mature dendritic cells derived from X-irradiated human monocytes depends on the type of maturation stimulus used.
abstract: Dendritic cells play an essential role in the immune system. We have previously reported that X-irradiated monocytes, precursors of dendritic cells, can differentiate into dendritic cells and then mature in terms of surface antigen expression after tumor necrosis factor-α stimulation, but show reduced functionality. Dendritic cells can mature in response to various types of maturation stimuli. Therefore, this study investigated whether dendritic cells from monocytes exposed to ionizing radiation can adequately respond to pathogen-derived components and proinflammatory cytokines. Human monocytes separated from buffy coats were exposed to X rays, and were then differentiated into immature dendritic cells. Immature dendritic cells were stimulated by lipopolysaccharide (LPS) or proinflammatory cytokine mixture. The dendritic cells from nonirradiated and X-irradiated monocytes showed maturation after LPS and proinflammatory cytokine mixture stimulation as confirmed by findings of surface antigen expression. Upon LPS stimulation, however, the expression levels of CD80 and CD83 on dendritic cells from X-irradiated monocytes were lower than those of dendritic cells from nonirradiated monocytes. Such reductions were not observed upon proinflammatory cytokine mixture stimulation. Similarly, an impairment of matrix metalloproteinase-9 and cytokine production was observed in LPS-stimulated dendritic cells from X-irradiated monocytes, whereas these impairments were not observed upon proinflammatory cytokine mixture stimulation. The ability of dendritic cells to stimulate T cells was lower in the irradiated group compared with the nonirradiated group despite the type of maturation stimulus. Thus, the present study suggests that the influence of X irradiation on the maturation of dendritic cells depends on the type of maturation stimulus used and that X irradiation impairs the response of dendritic cells to LPS.
authors.affiliation: Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshino
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D000954:Antigens, Surface / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000032:analysis; D014965:X-Rays
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D020780:Matrix Metalloproteinase 9