S K Chapes

Kansas State University, Manhattan, KS, United States

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Publications (90)262.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue macrophages are a heterogeneous collection of classically activated (M1) and alternatively activated (M2) macrophages. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, secreted by a variety of cell types including M2 macrophages. We generated a macrophage cell line stably overexpressing IL-10 (C2D-IL10) and analyzed the C2D-IL10 cells for several macrophage markers after exposure to adipocytes compared to C2D cells transfected with an empty vector (C2D-vector). C2D-IL10 macrophage cells expressed more CD206 when co-cultured with adipocytes than C2D-vector cells; while the co-cultured cell mixture also expressed higher levels of Il4, Il10, Il1β and Tnf. Since regular C2D cells traffic to adipose tissue after adoptive transfer, we explored the impact of constitutive IL-10 expression on C2D-IL10 macrophages in adipose tissue in vivo. Adipose tissue-isolated C2D-IL10 cells increased the percentage of CD206(+), CD301(+), CD11c(-)CD206(+) (M2) and CD11c(+)CD206(+) (M1b) on their cell surface, compared to isolated C2D-vector cells. These data suggest that the expression of IL-10 remains stable, alters the C2D-IL10 macrophage cell surface phenotype and may play a role in regulating macrophage interactions with the adipose tissue.
    PLoS ONE 01/2014; 9(1):e86541. · 3.53 Impact Factor
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    ABSTRACT: Obesity is characterized by an increased recruitment of pro-inflammatory macrophages to the adipose tissue (AT) leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimeric C57BL/6J mice reconstituted with either leptin receptor-deficient (db/db) or wild type (WT) bone marrow and challenged them with a high fat diet (HFD) for sixteen weeks. Mice reconstituted with db/db bone marrow (WT/db), had significantly lower body weight and adiposity compared to mice with WT bone marrow (WT/WT). Gonadal AT in WT/db mice displayed a two-fold lower expression of the inflammatory genes Tnfa, Il6 and Ccl2. In addition, gonadal fat of WT/db mice contained significantly fewer crown-like structures (CLS) compared to WT/WT mice and most of their AT macrophages (ATMs) expressed Mgl1 and were CCR2 negative, indicative of an anti-inflammatory phenotype. Moreover, WT/db mice exhibited greater insulin sensitivity compared to WT/WT mice. These data show that disrupted leptin signaling in bone marrow-derived cells attenuates the pro-inflammatory conditions that mediate many of the metabolic complications that characterize obesity. Our findings establish a novel mechanism involved in the regulation of obesity-associated systemic inflammation and support the hypothesis that leptin is a pro-inflammatory cytokine.
    Endocrinology 10/2013; · 4.72 Impact Factor
  • Stephen K Chapes, M Teresa Ortega
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    ABSTRACT: In preparation for a space flight on STS-126, two in vitro culture systems were used to investigate macrophage colony stimulating factor-dependent macrophage differentiation from mouse primary bone marrow cells. The patented Techshot Cell Cult Bioreactor and the BioServe Fluid Processing Apparatus (FPA) were operated in different orientations to determine their impact on macrophage growth and differentiation. Bone marrow cell parameters were determined after cells were grown in FPAs incubated at 37°C in vertical or horizontal orientations, and macrophage cell recovery was significantly higher from FPAs that were incubated in the horizontal orientation compared to "vertical" FPAs. Similarly, when bone marrow cells were grown in the Techshot bioreactor, there were significant differences in the numbers of macrophages recovered after 7 days, depending on movement and orientation of the bioreactor. Macrophage recovery was highest when the patented bioreactor was rotated in the horizontal, x-axis plane (merry-go-round fashion) compared to static and vertically, y-axis plane rotated (Ferris wheel fashion) bioreactors. In addition, the expression of F4/80 and other differentiation markers varied depending on whether macrophages differentiated in FPAs or in bioreactors. After 7 days, significant differences in size, granularity and molecule expression were seen even when the same primary bone marrow cells were used to seed the cultures. These data show that culture outcomes are highly dependent on the culture device and device orientation. Moreover, the impact of the culture system needs to be understood in order to interpret space flight data.
    Recent patents on space technology. 06/2013; 3(1):40-47.
  • Rishi Drolia, Tonia Von Ohlen, Stephen K Chapes
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    ABSTRACT: Ehrlichia chaffeensis is a Gram-negative, obligate intracellular bacterium which causes the tick-borne disease human monocytic ehrlichiosis. In vertebrates, E. chaffeensis replicates in monocytes and macrophages. However, no clear cell or tissue tropism has been defined in arthropods. Our group identified two host genes that control E. chaffeensis replication and infection in vivo in Drosophila, Uridine cytidine kinase and separation anxiety. Using the UAS-GAL4 RNAi system, we generated F1 flies (UAS-gene of interestRNAi x tissue-GAL4 flies) that have Uck2 or san silenced in ubiquitous or tissue-specific fashion. When Uck2 or san were suppressed in the hemocytes or in the fat body, E. chaffeensis replicated poorly and caused significantly less severe infections. Silencing of these genes in the eyes, wings, or the salivary glands did not impact fly susceptibility or bacterial replication. Our data suggest that in Drosophila, E. chaffeensis replicates within the hemocytes, the insect homolog of mammalian macrophages, and in the fat body, the liver homolog of mammals.
    International journal of medical microbiology: IJMM 01/2013; · 4.54 Impact Factor
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    ABSTRACT: Cell lines CΔ2+ and CΔ2- were developed from monocytes obtained from a 10-month-old, crossbred, female pig. These cells morphologically resembled macrophages, stained positively for α-naphthyl esterase and negatively for peroxidase. The cell lines were bactericidal and highly phagocytic. Both cell lines expressed the porcine cell-surface molecules MHCI, CD11b, CD14, CD16, CD172, and small amounts of CD2; however, only minimal amounts of CD163 were measured. The lines were negative for the mouse marker H2K(k), bovine CD2 control, and secondary antibody control. Additionally, cells tested negative for Bovine Viral Diarrhea Virus and Porcine Circovirus Type 2. Therefore, these cells resembled porcine macrophages based on morphology, cell-surface marker phenotype, and function and will be useful tools for studying porcine macrophage biology.
    Results in immunology. 01/2013; 3:26-32.
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    Stephen K Chapes, Sarah E Velasquez
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    ABSTRACT: The Kansas IDeA Network of Biomedical Research Excellence (K-INBRE) was established in 2001 and is a network of 10 higher-education institutions in Kansas and northern Oklahoma. The program is funded by the Institutional Development Award (IDeA) program of the National Institutes of Health (NIH). As part of the program's goal to enhance the research infrastructure in Kansas, a training program was developed to encourage undergraduates to participate in biomedical research. From September 2002 to May 2012, the K-INBRE supported 731 students at 10 institutions. Although 16% of student participants in the program are still undergraduates, 323 of our students have gone into biomedical graduate school or medical school programs. Thirty-seven percent of all the completed students have matriculated into graduate programs and 19% of our completed students went to medical school. Moreover, 12% have gone into other health-related professions. One percent of our students who went into medical school programs are in highly prestigious MD/PhD programs. In the fall of 2011, we surveyed participants from the last 10 years about career choices and the impact of the K-INBRE program on those students. Two hundred twenty-four former and current students responded to the survey with a consensus of high impact of the K-INBRE program on student training, career choices, and perceptions about research.
    Journal of microbiology & biology education : JMBE. 01/2013; 14(1):47-57.
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    ABSTRACT: Ehrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on Drosophila melanogaster S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the "permissive" genes for the ability to support Ehrlichia replication. Three additional D. melanogaster fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes CG6479, separation anxiety, chitinase 11, CG6364 (Uck2), CG6543 (Echs1), withered (whd), CG15881 (Ccdc58), CG14806 (Apop1), CG11875 (Nup37), and dumpy (dp) had increased resistance to infection with Ehrlichia. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (san, Cht11, Uck2, Echs1, whd, Ccdc58, and Apop1) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human UCK2 gene indicates that the disruption of the uridine-cytidine kinase affects E. chaffeensis replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for E. chaffeensis replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides.
    Infection and immunity 07/2012; 80(10):3576-86. · 4.21 Impact Factor
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    M Teresa Ortega, Nanyan Lu, Stephen K Chapes
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    ABSTRACT: We differentiated mouse bone marrow cells in the presence of recombinant macrophage colony stimulating (rM-CSF) factor for 14 days during the flight of space shuttle Space Transportation System (STS)-126. We tested the hypothesis that the receptor expression for M-CSF, c-Fms was reduced. We used flow cytometry to assess molecules on cells that were preserved during flight to define the differentiation state of the developing bone marrow macrophages; including CD11b, CD31, CD44, Ly6C, Ly6G, F4/80, Mac2, c-Fos as well as c-Fms. In addition, RNA was preserved during the flight and was used to perform a gene microarray. We found that there were significant differences in the number of macrophages that developed in space compared to controls maintained on Earth. We found that there were significant changes in the distribution of cells that expressed CD11b, CD31, F4/80, Mac2, Ly6C and c-Fos. However, there were no changes in c-Fms expression and no consistent pattern of advanced or retarded differentiation during space flight. We also found a pattern of transcript levels that would be consistent with a relatively normal differentiation outcome but increased proliferation by the bone marrow macrophages that were assayed after 14 days of space flight. There also was a surprising pattern of space flight influence on genes of the coagulation pathway. These data confirm that a space flight can have an impact on the in vitro development of macrophages from mouse bone marrow cells.
    Advances in Space Research 05/2012; 49(10):1441-1455. · 1.18 Impact Factor
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    ABSTRACT: There are still questions about whether macrophage differentiation is predetermined or is induced in response to tissue microenvironments. C2D macrophage cells reside early in the macrophage lineage in vitro, but differentiate to a more mature phenotype after adoptive transfer to the peritoneal cavity (PEC-C2D). Since C2D macrophage cells also traffic to adipose tissue after adoptive transfer, we explored the impact of white adipose tissue (WAT), brown adipose tissue (BAT) and in vitro cultured adipocytes on C2D macrophage cells. When PEC-C2D macrophage cells were cultured with preadipocytes the cells stretched out and CD11b and Mac-2 expression was lower compared to PEC-C2D macrophage cells placed in vitro alone. In contrast, PEC-C2D cells co-cultured with adipocytes maintained smaller, round morphology and more cells expressed Mac-2 compared to PEC-C2D co-cultured with preadipocytes. After intraperitoneal injection, C2D macrophage cells migrated into both WAT and BAT. A higher percentage of C2D macrophage cells isolated from WAT (WAT-C2D) expressed Ly-6C (33%), CD11b (11%), Mac-2 (11%) and F4/80 (29%) compared to C2D macrophage cells isolated from BAT (BAT-C2D). Overall, BAT-C2D macrophage cells had reduced expression of many cytokine, chemokine and receptor gene transcripts when compared to in vitro grown C2D macrophages, while WAT-C2D macrophage cells and PEC-C2D up-regulated many of these gene transcripts. These data suggest that the C2D macrophage phenotype can change rapidly and distinct phenotypes are induced by different microenvironments.
    Cellular Immunology 06/2011; 271(1):124-33. · 1.74 Impact Factor
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    ABSTRACT: CD81 is an integral membrane protein in the tetraspanin superfamily that serves as an adaptor protein. CD81 is also a maternally imprinted gene that is found in a regulated cluster of genes on mouse chromosome 7. Among offspring produced from heterozygous breeding pairs, CD81(null/null) mice grew at the same rate as CD81(+/+) and CD81(+/null) mice. Because of an inhibition in sperm-egg fusion, CD81(null/null) female mice are much less fertile than CD81(+/+) and CD81(+/null) mice. However, no published study has detailed the effect of the male CD81 genotype on the genotype and sex distribution of offspring. We set up breeding pairs of heterozygotic (C.129-Cd81(tm1) N7) female mice and male mice with CD81(+/null), CD81(+/+), or CD81(null/null) genotypes. The survival and development of CD81(+/null), CD81(+/+), and CD81(null/null) offspring were monitored and compared. Compared with those of heterozygous male breeders, CD81(null/null) pups were born at a less-than-expected ratio from CD81(null/null) males. Sex distribution did not differ among pups sired by CD81(null/null) compared with CD81(+/null) mice. The data suggest that the effect of the CD81(null/null) paternal genotype on offspring is manifested early in development or in utero.
    Comparative medicine 06/2010; 60(3):196-9. · 1.12 Impact Factor
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    ABSTRACT: Obesity is associated with a proinflammatory state, with macrophage infiltration into adipose tissue. We tested the hypothesis that communication between macrophages and adipocytes affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function. To test this hypothesis, we cocultured 3T3-L1 adipocytes with C2D macrophages or primary peritoneal mouse macrophages and examined the impacts of macrophages and adipocytes on each other. Adipocytes and preadipocytes did not affect C2D macrophage TNF-alpha, IL-6, or IL-1beta transcript concentrations relative to those obtained when C2D macrophages were incubated alone. However, preadipocytes and adipocytes increased PEC-C2D macrophage IL-6 transcript levels, while preadipocytes inhibited IL-1beta transcript levels compared to those obtained when PEC-C2D macrophages were incubated in medium alone. We found that adipocyte coculture increased macrophage consumption of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and, in some cases, IL-6. C2D macrophages increasingly downregulated GLUT4 transcript levels in differentiated adipocytes. Recombinant TNF-alpha, IL-1beta, and IL-6 also downregulated GLUT4 transcript levels relative to those for the control. However, only IL-6 was inhibitory at concentrations detected in macrophage-adipocyte cocultures. IL-6 and TNF-alpha, but not IL-1beta, inhibited Akt phosphorylation within 15 min of insulin stimulation, but only IL-6 was inhibitory 30 min after stimulation. Lastly, we found that adipocyte differentiation was inhibited by macrophages or by recombinant TNF-alpha, IL-6, and IL-1beta, with IL-6 having the most impact. These data suggest that the interaction between macrophages and adipocytes is a complex process, and they support the hypothesis that the macrophage-adipocyte interaction affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function.
    Clinical and vaccine Immunology: CVI 02/2010; 17(4):651-9. · 2.60 Impact Factor
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    Alison Luce-Fedrow, Tonia Von Ohlen, Stephen K Chapes
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    ABSTRACT: Ehrlichia chaffeensis is an obligate, intracellular bacterium, transmitted by the tick Amblyomma americanum, and is the causative agent of human monocytic ehrlichiosis infections. We previously demonstrated that E. chaffeensis is capable of growing in Drosophila S2 cells. Therefore, we tested the hypothesis that E. chaffeensis can infect adult Drosophila melanogaster. Adult Drosophila organisms were experimentally challenged with intra-abdominal injections of bacteria. Ehrlichia-infected flies showed decreased survival compared to wild-type flies, and bacteria isolated from flies could reinfect mammalian macrophages. Ehrlichia infections activated both the cellular and humoral immune responses in the fly. Hemocytes phagocytosed bacteria after injection, and antimicrobial peptide pathways were induced following infection. Increased pathogenicity in flies carrying mutations in genes in both the Toll and Imd pathways suggests that both immune defense pathways participate in host defense. Induction of Drosophila cellular and humoral responses and the in vivo replication of E. chaffeensis suggests that D. melanogaster is a suitable host for E. chaffeensis. In the future, it will be a useful tool to unlock some of the in vivo mysteries of this arthropod-borne bacterium.
    Infection and immunity 09/2009; 77(11):4815-26. · 4.21 Impact Factor
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    ABSTRACT: 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 with ground (GRD) controls (P < 0.005). Splenic lymphocyte, monocyte/macrophage, 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 Escherichia coli, was decreased compared with GRD mice (P < 0.05). Secretion of IL-6 and IL-10, but not TNF-alpha, by LPS-stimulated splenocytes was increased in FLT mice (P < 0.05). Finally, many of the genes responsible for scavenging reactive oxygen species were upregulated after flight. These data indicate that exposure to the spaceflight environment can increase anti-inflammatory mechanisms and change the ex vivo response to LPS, a bacterial product associated with septic shock and a prominent Th1 response.
    Journal of Applied Physiology 04/2009; 106(6):1935-42. · 3.48 Impact Factor
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    ABSTRACT: Several tick-transmitted Anaplasmataceae family rickettsiales of the genera Ehrlichia and Anaplasma have been discovered in recent years. Some species are classified as pathogens causing emerging diseases with growing health concern for people. They include human monocytic ehrlichiosis, human granulocytic ewingii ehrlichiosis and human granulocytic anaplasmosis which are caused by Ehrlichia chaffeensis, E. ewingii and Anaplasma phagocytophilum, respectively. Despite the complex cellular environments and defense systems of arthropod and vertebrate hosts, rickettsials have evolved strategies to evade host clearance and persist in both vertebrate and tick host environments. For example, E. chaffeensis growing in vertebrate macrophages has distinct patterns of global host cell-specific protein expression and differs considerably in morphology compared with its growth in tick cells. Immunological studies suggest that host cell-specific differences in Ehrlichia gene expression aid the pathogen, extending its survival. Bacteria from tick cells persist longer when injected into mice compared with mammalian macrophage-grown bacteria, and the host response is also significantly different. This review presents the current understanding of tick-Ehrlichia interactions and implications for future.
    Frontiers in Bioscience 02/2009; 14:3259-73. · 3.29 Impact Factor
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    ABSTRACT: CD81 is an integral membrane protein belonging to the tetraspanin superfamily. It has two extracellular domains that interact with cell surface proteins and two intracellular tails that contribute to cellular processes. Although there are considerable data about how CD81 affects T- and B-cell function, not much is known about how it impacts macrophages. To address this, we established four cell lines from mouse bone marrow in the presence of macrophage colony-stimulating factor and transfection with SV40 large T antigen. Two were CD81(-/-) (ASD1 and ASD2) and two were CD81(+/-) (2ASD1.10 and 2BSD1.10). Cells were Mac-2-, PU.1-, and c-fms-positive and all the cell lines were phagocytic indicating that they were macrophage-like. In mixtures of the two cell types in tissue culture, CD81(-/-) cells out competed CD81(+/-) cells with CD81-bearing cells being undetectable after 50 cell culture passages. Although cell divisions during log-phase growth were not significantly different between CD81(+/-) macrophage cells and CD81(-/-) macrophage cells, we found that CD81(-/-) macrophage cells reached a higher density at confluency than CD81(+/-) macrophage cells. CD81 transcript levels increased as cultures became confluent, but transcript levels of other tetraspanin-related molecules remained relatively constant. Transfection of CD81 into ASD1 (CD81(-/-)) cells reduced the density of confluent cultures of transformants compared to cells transfected with vector alone. These data suggest that CD81 potentially plays a role in macrophage cell line growth regulation.
    In Vitro Cellular & Developmental Biology - Animal 02/2009; 45(5-6):213-25. · 1.29 Impact Factor
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    Stephen K Chapes, Roman R Ganta
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    ABSTRACT: Pathogenic bacteria belonging to the family Anaplasmataceae include species of the genera Ehrlichia and Anaplasma. Ehrlichia chaffeensis, first known as the causative agent of human monocytic ehrlichiosis, also infects several vertebrate hosts including white-tailed deer, dogs, coyotes and goats. E. chaffeensis is transmitted from the bite of an infected hard tick, such as Amblyomma americanum. E. chaffeensis and other tick-transmitted pathogens have adapted to both the tick and vertebrate host cell environments. Although E. chaffeensis persists in both vertebrate and tick hosts for long periods of time, little is known about that process. Immunological studies will be valuable in assessing how the pathogen persists in nature in both vertebrate and invertebrate hosts. Understanding the host immune response to the pathogen originating from dual host backgrounds is also important to develop effective methods of diagnosis, control and treatment. In this paper, we provide our perspective of the current understanding of the immune response against E. chaffeensis in relation to other related Anaplasmataceae pathogens.
    Veterinary Parasitology 01/2009; 158(4):344-59. · 2.38 Impact Factor
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    ABSTRACT: Bone marrow cells were isolated from the humeri of C57BL/6 mice after a 13-day flight on the space shuttle Space Transportation System (STS)-118 to determine how spaceflight affects differentiation of cells in the granulocytic lineage. We used flow cytometry to assess the expression of molecules that define the maturation/activation state of cells in the granulocytic lineage on three bone marrow cell subpopulations. These molecules included Ly6C, CD11b, CD31 (platelet endothelial cell adhesion molecule-1), Ly6G (Gr-1), F4/80, CD44, and c-Fos. The three subpopulations were small agranular cells [region (R)1], larger granular cells (R2), which were mostly neutrophils, and very large, very granular cells (R3), which had properties of macrophages. Although there were no composite phenotypic differences between total bone marrow cells isolated from spaceflight and ground-control mice, there were subpopulation differences in Ly6C (R1 and R3), CD11b (R2), CD31 (R1, R2, and R3), Ly6G (R3), F4/80 (R3), CD44(high) (R3), and c-Fos (R1, R2, and R3). In particular, the elevation of CD11b in the R2 subpopulation suggests neutrophil activation in response to landing. In addition, decreases in Ly6C, c-Fos, CD44(high), and Ly6G and an increase in F4/80 suggest that the cells in the bone marrow R3 subpopulation of spaceflight mice were more differentiated compared with ground-control mice. The presence of more differentiated cells may not pose an immediate risk to immune resistance. However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights.
    Journal of Applied Physiology 01/2009; 106(2):548-55. · 3.48 Impact Factor
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    ABSTRACT: Palmitoylation of tetraspanins affects protein–protein interactions, suggesting a key role in the assembly of the tetraspanin web. Since palmitoylation occurs on intracellular cysteine residues, we examined whether mutating these residues in the human tetraspanin CD81 would affect the association of CD81 with other surface membrane proteins. Mutation of at least six of the eight juxtamembrane cysteines was required to completely eliminate detectable CD81 palmitoylation, indicating that several sites can be palmitoylated. Interestingly, these mutated proteins exhibited reduced cell surface detection by antibody compared to wild-type CD81, but this was not due to differences in the level of protein expression, trafficking to the cell surface, protein stability, or anti-CD81 antibody binding affinity. Instead, the mutant CD81 proteins appeared to be partially hidden from detection by anti-CD81 antibody, presumably due to altered interactions with other proteins at the cell surface. Associations with the known CD81-interacting proteins CD9 and EWI-2 were also impaired with the mutant CD81 proteins. Taken together, these findings indicate that mutation of juxtamembrane cysteines alters the interaction of CD81 with other proteins, either because of reduced palmitoylation, structural alterations in the mutant proteins, or a combination of both factors, and this affects the CD81 microenvironment on the cell surface.
    Experimental Cell Research 01/2009; · 3.56 Impact Factor
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    ABSTRACT: 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-gamma, and macrophage inflammatory protein-1alpha 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.
    Journal of Applied Physiology 12/2008; 106(1):194-202. · 3.48 Impact Factor
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    Betsey E Potts, Stephen K Chapes
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    ABSTRACT: Macrophage function depends on their in situ location. To test this hypothesis, we examined functional changes of the C2D macrophage cell line after adoptive transfer. In vitro, C2D macrophages reside early in the macrophage lineage and show little functional activity. After in vivo i.p. culture, C2D macrophage cells switch their cytokine/chemokine profile from primarily Th2 cytokines produced in vitro to a Th1 profile including MIP-1alpha, IL-6, and TNF-alpha. The in vivo environment also caused C2D macrophage cells to become more phagocytic than their in vitro counterparts. These data indicate that C2D macrophage cells exhibit distinct functions because of in vivo signals that are absent during in vitro culture.
    Journal of Leukocyte Biology 04/2008; 83(3):602-9. · 4.57 Impact Factor

Publication Stats

949 Citations
262.64 Total Impact Points

Institutions

  • 1988–2013
    • Kansas State University
      • • Division of Biology
      • • Department of Diagnostic Medicine/Pathobiology
      Manhattan, KS, United States
  • 2010
    • University of Liverpool
      • Department of Cellular and Molecular Physiology
      Liverpool, England, United Kingdom
  • 2002
    • University of Colorado at Boulder
      • Department of Aerospace Engineering Sciences (AES)
      Boulder, CO, United States