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Thank you for visiting our website. We are a relatively small lab with big ideas. We are part of a much larger group of investigators known collectively as the LLUMC Molecular Radiation Biology Laboratories. It is our hope that this website will educate, communicate, and incite scientific debate. As the PI of our little group, I hope to post our data and discuss potential mechanisms, consequences, and countermeasures. With a bit of luck we'll all learn something. The links to the left include our merry band as well as collaborating investigators and laboratories. The links to the right include our archive and blogroll. The banner above will always bring you back to the main page page. Take a look around and please feel free to leave a comment on our blog (try to keep it civil and constructive) or shoot us an e-mail. - Michael " Ubertramp " Pecaut
Lab Update
Posted by: Ubertramp on 2009.04.12
Categories & Tags: Gamma Radiation,Grant,Low Dose Radiation,Microgravity,NASA,New Publication,Protons,Radiation,Space Shuttle,T cell
Comments: None
It’s been a couple of months since the last update, so it’s about time. We have some good news and some bad news. The bad news first. My NASA grant was turned down for funding. I haven’t seen the review yet, so I’m not sure why. Nor do I know who or what actually DID get funded. Guess we’ll have to see.
Ironically (or coincidentally, I haven’t decided which), we received the acceptance letter from JAP for our third immune publication from the last shuttle flight on the same day. The reviewers were pretty rough on us, though. It bounced back and forth three times before they finally accepted it. Farnaz was pretty excited as this was her first publication. Woot! Now all she has to do is finish her dissertation and graduate. Hahaha. It’s still an Epub ahead of print, so I don’t have a reprint. Give it a few weeks. For now, here’s the abstract.
Effects of spaceflight on innate immune function and antioxidant gene expression.
Baqai FP, Gridley DS, Slater JM, Luo-Owen X, Stodieck LS, Ferguson VL, Chapes SK, Pecaut MJ.
Spaceflight conditions have a significant impact on a number of physiological functions due to psychological stress, radiation and reduced gravity. To explore the effect of the flight environment on immunity, C57BL/6NTac mice were flown on a 13-day space shuttle mission (STS-118). In response to flight, animals had a reduction in liver, spleen and thymus masses compared to ground (GRD) controls (p<0.005). Splenic lymphocytes, monocyte/macrophages and granulocyte counts were significantly reduced in the flight (FLT) mice (p<0.05). Although spontaneous blastogenesis of splenocytes in FLT mice was increased, response to lipopolysaccharide (LPS), a B cell mitogen derived from E. coli, was decreased compared to GRD mice (p<0.05). Secretion of IL-6 and IL-10, but not that of TNF-alpha by LPS-stimulated splenocytes was increased in FLT mice (p<0.05). Finally, many of the genes responsible for scavenging ROS were up-regulated after flight. These data indicate that exposure to the spaceflight environment can increase anti-inflammatory mechanisms and change the ex vivo response to lipopolysaccharide (LPS), a bacterial product associated with septic shock and a prominent Th1 response.
Daila also had two additional publications. One on protons and one on photons, but both T cell gene expression. Here are those abstracts.
Gridley DS, Rizvi A, Luo-Owen X, Makinde AY, Pecaut MJ.
A better understanding of low dose radiation effects is needed to accurately estimate health risks. In this study, C57BL/6 mice were gamma-irradiated to total doses of 0, 0.01, 0.05, and 0.1 Gy ((57)Co; ~0.02 cGy/h). Subsets per group were euthanized at the end of irradiation (day 0) and on days 4 and 21 thereafter. Relative spleen mass and splenic white blood cell (WBC) counts, major leukocyte populations, and spontaneous DNA synthesis were consistently higher in the irradiated groups on day 0 compared to 0 Gy controls, although significance was not always obtained. In the spleen, all three major leukocyte types were significantly elevated on day 0 (P < 0.05). By day 21 post-irradiation the T, B, and natural killer (NK) cell counts, as well as CD4(+) T cells and CD4:CD8 T cell ratio, were low especially in the 0.01 Gy group. Although blood analyses showed no significant differences in leukocyte counts or red blood cell and platelet characteristics, the total T cells, CD4(+) T cells, and NK cells were increased by day 21 after 0.01 Gy (P < 0.05). Gene analysis of CD4(+) T cells negatively isolated from spleens on day 0 after 0.1 Gy showed significantly enhanced expression of Il27 and Tcfcp2, whereas Inha and Socs5 were down-regulated by 0.01 Gy and 0.1 Gy, respectively (P < 0.05). A trend for enhancement was noted in two additional genes (Il1r1 and Tbx21) in the 0.1 Gy group (P < 0.1). The data show that protracted low dose photons had dose- and time-dependent effects on CD4(+) T cells after whole-body exposure.
Low-dose, low-dose-rate proton radiation modulates CD4(+) T cell gene expression.
Gridley DS, Pecaut MJ, Rizvi A, Coutrakon GB, Luo-Owen X, Makinde AY, Slater JM.
Purpose: To evaluate cluster of differentiation 4(+) (CD4(+)) T cell gene expression and related parameters after whole-body exposure to proton radiation as it occurs in the spaceflight environment. Materials and methods: C57BL/6 mice were irradiated to total doses of 0, 0.01, 0.05, and 0.1 gray (Gy) at 0.1 cGy/h. On day 0 spleens were harvested from a subset in the 0, 0.01 and 0.1 Gy groups; (CD4(+)) T cells were isolated; and expression of 84 genes relevant to T helper (Th) cell function was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). Remaining mice were euthanized on days 0, 4, and 21 for additional analyses. Results: Genes with >2-fold difference and p < 0.05 compared to 0 Gy were noted. After 0.01 Gy, five genes were up-regulated (Ccr5, Cd40, Cebpb, Igsf6, Tnfsf4) and three were down-regulated (Il4ra, Mapk8, Nfkb1). After 0.1 Gy there were nine up-regulated genes (Ccr4, Cd40, Cebpb, Cxcr3, Socs5, Stat4, Tbx21, Tnfrsf4, Tnfsf4); none were down-regulated. On day 0 after 0.01 Gy, CD4(+) T cell counts and CD4:CD8 ratio were low in the spleen (p < 0.05). Spontaneous DNA synthesis in both spleen and blood was lowest in the 0.01 Gy group on day 0; on days 4 and 21 all p values were >0.1. Conclusion: The data show that the pattern of gene expression in CD4(+) T cells after protracted low-dose proton irradiation was significantly modified and highly dependent upon total dose. The findings also suggest that low-dose radiation, especially 0.01 Gy, may enhance CD4(+) T cell responsiveness.
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