title: Acute effects of iron-particle radiation on immunity. Part II: Leukocyte activation, cytokines and adhesion.
abstract: The effects of high-linear energy transfer (LET) radiation on immune function have not been clearly established. The major goal of this study was to evaluate leukocyte responses after whole-body exposure to high-LET radiation. C57BL/6 mice were exposed to 0, 0.5, 2 and 3 Gy (56)Fe(26+) particles (1055 MeV/nucleon, 148.2 keV/microm) and killed humanely 4 days after exposure. Spontaneous synthesis of DNA in blood and spleen cells was increased significantly in groups receiving either 2 or 3 Gy (P < 0.001). In contrast, a significant depression in the response of T lymphocytes to phytohemagglutinin (PHA) and concanavalin A (ConA) was noted (P < 0.005); the response to lipopolysaccharide (LPS), a B-cell mitogen, was similar among groups. A cytometric bead array assay revealed that the level of tumor necrosis factor alpha (Tnfa) secreted by splenocytes increased significantly with increasing (56)Fe-particle dose (P < 0.05); interferon gamma, interleukin2 (Il2), Il4 and Il5 were unaffected. Flow cytometry analysis showed that 2 and 3 Gy markedly reduced splenic mononuclear cells expressing the activation markers CD25 and CD71, both with and without the T-cell marker CD3 (P < 0.05); proportions also varied significantly. Similar patterns were noted in mononuclear and granular cells with adhesion markers CD11b and, to a lesser extent, CD54 (P < 0.05). The results show that a single, acute exposure to high-LET radiation induced changes that can profoundly alter leukocyte functions. The implications of the data are discussed in relation to low-LET radiation, altered gravity, and space flight.
authors.affiliation: Department of Radiation Medicine, Radiobiology Program, Loma Linda University and Medical Center, CA 92354, USA. dgridley@dominion.llumc.edu
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Radha
authors.initials: R
authors.lastname: Dutta-Roy
authors.forename: Melba L
authors.initials: ML
authors.lastname: Andres
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000528:radiation effects; D016207:Cytokines / Q000276:immunology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007113:Immunity, Innate / Q000528:radiation effects; D007503:Iron Isotopes / Q000633:toxicity*; D007962:Leukocytes / Q000276:immunology* / Q000528:radiation effects*; D018499:Linear Energy Transfer; D008213:Lymphocyte Activation / Q000276:immunology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D007503:Iron Isotopes