scholarly journals Spaceflight effects on T lymphocyte distribution, function and gene expression

2009 ◽  
Vol 106 (1) ◽  
pp. 194-202 ◽  
Author(s):  
Daila S. Gridley ◽  
James M. Slater ◽  
Xian Luo-Owen ◽  
Asma Rizvi ◽  
Stephen K. Chapes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Distribution Function ◽  
Nk Cells ◽  
Space Shuttle ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Cell Counts ◽  
Inflammatory Protein ◽  
Highly Sensitive ◽  
Macrophage Inflammatory Protein

The immune system is highly sensitive to stressors present during spaceflight. The major emphasis of this study was on the T lymphocytes in C57BL/6NTac mice after return from a 13-day space shuttle mission (STS-118). Spleens and thymuses from flight animals (FLT) and ground controls similarly housed in animal enclosure modules (AEM) were evaluated within 3–6 h after landing. Phytohemagglutinin-induced splenocyte DNA synthesis was significantly reduced in FLT mice when based on both counts per minute and stimulation indexes ( P < 0.05). Flow cytometry showed that CD3+ T and CD19+ B cell counts were low in spleens from the FLT group, whereas the number of NK1.1+ natural killer (NK) cells was increased ( P < 0.01 for all three populations vs. AEM). The numerical changes resulted in a low percentage of T cells and high percentage of NK cells in FLT animals ( P < 0.05). After activation of spleen cells with anti-CD3 monoclonal antibody, interleukin-2 (IL-2) was decreased, but IL-10, interferon-γ, and macrophage inflammatory protein-1α were increased in FLT mice ( P < 0.05). Analysis of cancer-related genes in the thymus showed that the expression of 30 of 84 genes was significantly affected by flight ( P < 0.05). Genes that differed from AEM controls by at least 1.5-fold were Birc5, Figf, Grb2, and Tert (upregulated) and Fos, Ifnb1, Itgb3, Mmp9, Myc, Pdgfb, S100a4, Thbs, and Tnf (downregulated). Collectively, the data show that T cell distribution, function, and gene expression are significantly modified shortly after return from the spaceflight environment.

Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression

1999 ◽  
Vol 277 (3) ◽  
pp. L498-L510 ◽  
Author(s):  
Janice A. Dye ◽  
Kenneth B. Adler ◽  
Judy H. Richards ◽  
Kevin L. Dreher
Keyword(s):  
Gene Expression ◽  
Fly Ash ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Tracheal Epithelial Cells ◽  
Inflammatory Protein ◽  
Tracheal Epithelial ◽  
Oil Fly Ash ◽  
Dose Dependent ◽  
Macrophage Inflammatory Protein

Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.

Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses

1999 ◽  
Vol 86 (6) ◽  
pp. 2065-2076 ◽  
Author(s):  
Stephen K. Chapes ◽  
Steven J. Simske ◽  
Gerald Sonnenfeld ◽  
Edwin S. Miller ◽  
Robert J. Zimmerman
Keyword(s):  
Peritoneal Macrophage ◽  
Space Shuttle ◽  
Marrow Cell ◽  
Interleukin 2 ◽  
Plasma Corticosterone ◽  
Interferon Γ ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Immunological Parameters ◽  
Immunological Responses

Sprague-Dawley rats were subjected to two 8-day spaceflights on the space shuttle. Rats housed in the National Aeronautics and Space Administration’s animal enclosure were injected (iv or sc) with pegylated interleukin-2 (PEG-IL-2) or a placebo. We tested the hypothesis that PEG-IL-2 would ameliorate some of the effects of spaceflight. We measured body and organ weights; blood cell differentials; plasma corticosterone; colony-forming units (macrophage and granulocyte macrophage); lymphocyte mitogenic, superantigenic, and interferon-γ responses; bone marrow cell and peritoneal macrophage cytokine secretion; and bone strength and mass. Few immunological parameters were affected by spaceflight. However, some spaceflight effects were observed in each flight. Specifically, peritoneal macrophage spontaneous secretion of tumor necrosis factor-α occurred in the first but not in the second flight. A significant monocytopenia and lymphocytopenia were detected in the second but not in the first flight. The second mission produced bone changes more consistent with past spaceflight investigations. PEG-IL-2 did not appear to be beneficial; however, this was mostly due to the lack of spaceflight effects. These studies reflect the difficulty in reproducing experimental models by using current space shuttle conditions.

scholarly journals Primary naïve and interleukin-2-activated natural killer cells do not support efficient ectromelia virus replication

2008 ◽  
Vol 89 (3) ◽  
pp. 751-759 ◽  
Author(s):  
April Keim Parker ◽  
Wayne M. Yokoyama ◽  
John A. Corbett ◽  
Nanhai Chen ◽  
R. Mark L. Buller
Keyword(s):  
Gene Expression ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Early Gene ◽  
Progeny Virus ◽  
Ectromelia Virus

Natural killer (NK) cells are known for their ability to lyse tumour cell targets. Studies of infections by a number of viruses, including poxviruses and herpesviruses, have demonstrated that NK cells are vital for recovery from these infections. Little is known of the ability of viruses to infect and complete a productive replication cycle within NK cells. Even less is known concerning the effect of infection on NK cell biology. This study investigated the ability of ectromelia virus (ECTV) to infect NK cells in vitro and in vivo. Following ECTV infection, NK cell gamma interferon (IFN-γ) production was diminished and infected cells ceased proliferating and lost viability. ECTV infection of NK cells led to early and late virus gene expression and visualization of immature and mature virus particles, but no detectable increase in viable progeny virus. It was not unexpected that early gene expression occurred in infected NK cells, as the complete early transcription system is packaged within the virions. The detection of the secreted early virus-encoded immunomodulatory proteins IFN-γ-binding protein and ectromelia inhibitor of complement enzymes (EMICE) in NK cell culture supernatants suggests that even semi-permissive infection may permit immunomodulation of the local environment.

Dual Control of Human Interleukin-2 and Interferon-γ Gene Expression by Histamine: Activation and Suppression

1996 ◽  
Vol 170 (1) ◽  
pp. 149-155 ◽  
Author(s):  
G. Arad ◽  
R. Nussinovich ◽  
M. Na’amad ◽  
R. Kaempfer
Keyword(s):  
Gene Expression ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Dual Control

Aberrant regulation of interleukin-2 but not of interferon-γ gene expression in Down syndrome (trisomy 21)

1991 ◽  
Vol 58 (2) ◽  
pp. 251-266 ◽  
Author(s):  
Lisya Gerez ◽  
Liora Madar ◽  
Gila Arad ◽  
Teresa Sharav ◽  
Ayelet Reshef ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Trisomy 21 ◽  
Interleukin 2 ◽  
Interferon Γ

scholarly journals Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 118-124 ◽  
Author(s):  
M Chang ◽  
Y Suen ◽  
SM Lee ◽  
D Baly ◽  
JS Buzby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Altered Expression ◽  
Inflammatory Protein ◽  
Growth Factor Beta ◽  
Macrophage Inflammatory Protein

Hematopoiesis is developmentally immature in the newborn compared with the adult. Diminished gene expression of several positive hematopoietic regulators has been observed in activated cord compared with adult peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362, 1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered expression of negative hematopoietic regulators during states of increased demand may also contribute to the pathogenesis of newborn dyshematopoiesis. To test this hypothesis, we measured protein levels of transforming growth factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the conditioned media of human umbilical cord and adult MNC using specific enzyme-linked immunosorbent assays. There was significantly less TGF-beta 1 in culture supernatants of cord versus adult MNC after 24, 72, and 120 hours of stimulation (P < .05), and significantly less MIP-1 alpha in cord versus adult supernatants after 72 hours and 120 hours of stimulation (P < .01). We then examined the mRNA expression of the negative regulators TGF-beta 1, MIP-1 alpha, and interleukin-8 (IL-8) in cord and adult MNC using Northern blot hybridization followed by quantitative densitometry. Cord MNC expressed significantly less TGF- beta 1 mRNA than adult MNC 6 hours and 72 hours after stimulation (P < .001). Cord MNC expressed significantly less MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P < .001), and 72 hours after stimulation (P < .001). Cord MNC also expressed significantly less IL-8 mRNA than adult MNC 6 hours after stimulation (P < .001). Therefore, decreased mRNA accumulation appears to coincide with reduced cytokine expression in the activated cord MNC. There were no significant differences in the transcription rates determined by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in cord versus adult MNC after 6 hours of stimulation, suggesting that the reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be secondary to alteration in posttranscriptional regulation. The present results, together with those of our previous studies, suggest that the altered expression of both positive and negative hematopoietic regulators may be involved in the immaturity of host defense in human neonates.

Expression of Macrophage Inflammatory Protein-1 Receptors in Human CD34+ Hematopoietic Cells and Their Modulation by Tumor Necrosis Factor- and Interferon-γ

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3073-3081 ◽  
Author(s):  
Jan Dürig ◽  
Erika A. de Wynter ◽  
Christoph Kasper ◽  
Michael A. Cross ◽  
James Chang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Necrosis ◽  
Hematopoietic Cells ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Inflammatory Protein ◽  
Cd34 Cells ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

Abstract Macrophage inflammatory protein-1 (MIP-1) can stimulate growth inhibitory and potent chemotactic functions in hematopoietic cells. To investigate whether the action of MIP-1 may be regulated at the cellular receptor level, we studied the expression and modulation of MIP-1 receptors on CD34+ cells isolated from normal bone marrow (NBM), umbilical cord blood (CB), and leukapheresis products (LP). Expression of MIP-1 receptors on CD34+cells was analyzed by two-color flow cytometry using a biotinylated MIP-1 molecule. The mean percentage of LP CD34+ cells expressing the MIP-1 receptors was 67.7 ± 7.2% (mean ± SEM; n = 22) as compared with 89.9 ± 2.6% (n = 10) and 74.69 ± 7.04% (n = 10) in CB and NBM, respectively (P = .4). The expression of the MIP-1 receptor subtypes on LP CD34+ cells was studied by indirect immunofluorescence using specific antibodies for the detection of CCR-1, CCR-4, and CCR-5. Microscopical examination revealed a characteristic staining of the cytoplasmic cell membrane for all three receptor subtypes. Detailed analysis of two LP samples showed that 65.8%, 4.4%, and 30.5% of CD34+ cells express CCR-1, CCR-4, and CCR-5, respectively. Culture of LP CD34+ cells for 24 to 36 hours in the presence of tumor necrosis factor- (TNF-) and interferon-γ (IFN-γ) resulted in a significant increase in MIP-1 receptor expression. TNF- induced MIP-1 receptor upregulation in a time- and concentration-dependent manner. Our results suggest that inhibitory cytokines produced by the bone marrow microenvironment are likely to be involved in the regulation of MIP-1 receptor expression on hematopoietic cells. © 1998 by The American Society of Hematology.

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