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Biomedical subjects

R R Dietert

Publications and source records attributed to R R Dietert.

At least 19 recordsLinked to original sources
PubMed1999

Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity.

Meso-2,3-dimercaptosuccinic acid (DMSA) is a drug currently employed for cheltion therapy in lead poisoning; however, little is known about its potential effects on the immune system. To examine the effect of DMSA and its capacity to reverse immunotoxicity resulting from exposure to lead in utero, female Fischer 344 rats were administered lead acetate in drinking water from 2 weeks prior to mating until parturition; DMSA was given by gavage on days 6-21 of gestation. The immune function of the female offspring was tested at 13 weeks of age. The results showed that lead (250 ppm) suppressed Th1-type responses (delayed-type hypersensitivity (DTH), interferon gamma (IFN gamma) production), enhanced a Th2-type response (interleukin-4 (IL-4) production), and increased tumor necrosis factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg per day) during pregnancy significantly lowered the blood lead levels of both the embryos and the lactating dams as well as the milk lead level of lactating dams. The chelation treatment also reversed the lead-induced alterations in pup body weight, relative spleen weight, TNF alpha, and IL-4 production. But in utero exposure to DMSA alone resulted in decreased DTH response in adult offspring. This was likely due to a reduced cell recruitment, since plasma monocyte chemoattractant protein-1 (MCP-1) levels were decreased. The DMSA-exposed offspring also demonstrated increased interleukin-2 (IL-2) production. These results suggest that DMSA reverses some of the lead-induced immunotoxicity; however, this treatment itself during embryonic development produces subsequent adult immunomodulation.

Animals↗
PubMed1999

Influence of dietary arginine concentration on lymphoid organ growth in chickens.

In vivo effects of graded dietary levels of arginine on the body and lymphoid organs were investigated using Cornell K strain chickens of the B15/B15 haplotype. Two-week-old birds were fed an arginine-deficient basal diet (0.53% arginine) supplemented with additional arginine (up to 1.0% L-arginine to the diet). At four weeks of age, body weight, lymphoid organ weight, and concentrations of amino acids in plasma were measured. Arginine supplementation produced significant increases in plasma arginine (from 200 nM in chicks fed the basal diet to 2,000 nM in chicks receiving the 1.5% arginine diet) and ornithine concentrations (from 17 nM in chicks fed the basal diet to 500 nM in chicks receiving the 1.5% arginine diet). The arginine-deficient diet reduced body weight gain (P < 0.0001) and thymus, spleen, and bursa of Fabricius weights (P < 0.05). In contrast to the bursa weight, the thymus and spleen weights, as percentages of body weight, were also decreased (P < 0.05). This study suggests that arginine markedly influences lymphoid organ development, with a more pronounced effect on the thymus and spleen than on the bursa of Fabricius.

Amino Acids↗
PubMed1998

Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats.

Lead has been shown to exert toxic effects during early development. In these in vivo and ex vivo experiments, the effect of lead on the immune system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water during breeding and pregnancy (exposure was discontinued at parturition). Offspring received no additional lead treatment after birth. Immune function was assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were not different from controls with respect to the immune endpoints used in these experiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effector function properties (tumor necrosis factor-alpha and nitric oxide production) were elevated in the 250 ppm group, while cell-mediated immune function was depressed, as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm group. Interferon-gamma levels were decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate that exposure of mothers to moderate levels of lead produces chronic immune modulation in their F344 rat offspring exposed in utero. Since the mothers were not susceptible to chronic immune alterations, a developmental bias to the immunotoxic effects of lead is indicated. The differences observed are consistent with the possibility that lead may bias T helper subset development and/or function, resulting in alterations in the balance among type 1 and type 2 immune responses.

Animals↗
PubMed1998

Avian macrophage metabolism.

This review considers the role of avian macrophages as a source of immune effector and immunoregulatory metabolites. Although considerable attention has been given to the importance of leukocytic cytokines, particularly the monokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta), metabolites produced by macrophages appear to be of equal importance in determining the progression of immune responses. The three metabolite categories that have received the greatest attention are the reactive oxygen species (ROS), the reactive nitrogen intermediates (RNI), and the eicosanoids. Additionally, the xenobiotic metabolites produced via cytochrome P450 activity mediate some immune-environmental interactions. Each of these four metabolite categories is subject to different requirements for metabolite production, and each has distinct effector functions. An understanding of macrophage metabolite regulation could allow improvements in avian health management and production via the effective control of metabolite production. The present review considers prior and recent information on the production of the metabolites by avian macrophages. Additionally, the potential ramifications of metabolite production and regulation are discussed.

Animals↗
PubMed1998

Chemical sensitivity and the immune system: a paradigm to approach potential immune involvement.

This paper approaches the issue of chemical sensitivity and the immune system though a consideration of established environmentally-induced immune alterations which have particular relevance to the broader topic of chemical sensitivity. Additionally, the report discusses the potential problems associated with prior narrow evaluation strategies for the assessment of environmentally-induced inflammation. A combined approach to assessment drawing upon biomarkers of both the immune and neurological systems is suggested. Such an approach recognizes the key roles which mediators of these two systems play in facilitating host inflammatory responses. The paper concludes with a discussion of the types of specific immune alterations which, from a mechanistic perspective, are likely to be involved with any linkage of chemical sensitivity to the immune system.

Environmental Exposure↗
PubMed1997

Characterization of leukotriene production in vivo and in vitro in resident and elicited peritoneal macrophages in chickens and mice.

Previously, we reported differences in arachidonic acid metabolism in elicited chicken peritoneal macrophages when compared with murine resident and elicited peritoneal macrophages. We now describe leukotriene (LT) production in the same systems, using resident (murine) and inflammatory macrophages (from both species). Inflammatory (4- or 42-g Sephadex-elicited) peritoneal macrophages from chickens lacked the capacity to produce LT in vivo (following opsonized zymosan [OZ] stimulation) or in vitro, in response to A23187. In addition, chicken macrophages were unable to metabolize exogenously added LTC4 or LTD4 in vitro. In contrast, resident murine peritoneal macrophages produced measurable quantities of LTs (in vivo) within 5 min with an 8-fold increase after 45 min. LTC4 was effectively converted to LTE4 in vivo in a time-dependent manner (65% LTC4/35% LTE4 after 5 min stimulation with OZ and 6% LTC4/94% LTE4 after 60 min stimulation), but no in vitro. The lack of LTC4 metabolism to LTE4 in vitro could not be explained by cell-cell interaction between adherent and nonadherent cells. LTD4 was not detected under any experimental condition. Murine peritoneal cells incubated with LTD4 (with or without agonist) produced LTE4 in a time-dependent fashion. Addition of L-cysteine (a dipeptidase inhibitor) did not explain the lack of detectable levels of LTD4 following intraperitoneal stimulation with OZ. These results suggest that elicited chicken peritoneal macrophages are incapable of producing LTs compared to murine peritoneal macrophages. In addition, these studies fail to explain the different product profiles with in vivo stimulation of murine peritoneal macrophages as compared to in vitro stimulation.

Animals↗
PubMed1996

Inhibition of nitric oxide synthase gene expression in vivo and in vitro by repeated doses of endotoxin.

We have examined the effects of repeated endotoxin administration in vivo and in vitro on the induction of nitric oxide synthase (NOS). In vivo, hepatic NOS activity and mRNA were increased markedly by the administration of Escherichia coli lipopolysaccharide (LPS). The change in hepatic NOS activity coincided with a marked accumulation of hepatic citrulline. Both enzyme activity and citrulline concentration returned to normal by 12 h after LPS administration. At this time, a subsequent administration of endotoxin caused no change in either NOS mRNA, NOS activity, or citrulline concentration, and thus an endotoxin-refractory state for nitric oxide (NO) synthesis was established. Normal sensitivity was reestablished by 24 h after the initial dose. In vitro studies using both a macrophage cell line (HD11) and primary macrophages indicated that LPS pretreatment caused cells in culture to become completely refractory to subsequent stimulation by LPS. Finally, we tested the hypothesis that NO may be involved in the development of the refractory state. Various inhibitors blocked the initial synthesis of NO by > 90% but failed to influence the development of the refractory state. Our study demonstrates both in vivo and in vitro that NO synthesis is completely blocked after repeated exposure to endotoxin by a mechanism that appears to be pretranslational. This model of early endotoxin tolerance may provide insight into the molecular mechanisms that regulate expression of the NOS gene.

Animals↗
PubMed1996

Toxicological considerations in evaluating indoor air quality and human health: impact of new carpet emissions.

This review article considers evidence regarding the toxicological impact of new carpet emissions on indoor air quality and human health. It compares emissions data from several studies and describes the dominant compounds found in those emissions. The toxicity of each these compounds is assessed for animal and human data, with a focus on inhalation exposure. Data for acute and chronic exposures are presented, and synergistic effects are considered. Differences and similarities between health responses caused by toxicity and/or by immunological reactions are discussed. Possible neurogenic pathways and associations between these and immune changes are considered as they might relate to inflammatory-based human reactions. Additionally, factors affecting human odor responses are described. The roles that a variety of psychological factors may also play in the etiology of potentially related phenomena, such as the sick building syndrome, pathogenic illness, and multiple chemical sensitivity, are considered. Gaps in the literature are identified within the article and suggestions for future research are offered. In particular, it is noted that few, if any, prior studies have evaluated both neurogenic and immune-mediated inflammation status within the same study. Based on the present information available, it is concluded that under normal environmental circumstances, VOC emissions from new carpets are sufficiently low such that they should not adversely affect indoor air quality or pose significant health risk to people.

Air Pollutants↗
PubMed1994

Nitric oxide (.NO)-induced mitochondrial injury among chicken .NO-generating and target leukocytes.

In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage cell lines, HD11 and MQ-NCSU, produced .NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of .NO produced. Using a modified MTT assay, .NO induced suppression in two mitochondrial complexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 +/- 5.5% suppression; complex II, 27.9 +/- 5.2%). In contrast, mitochondrial activities in samples receiving LPS plus inhibitor, NG-nitro-L-arginine methyl ester (NAME; 5 mM) or 2,4-diamino-6-hydroxypyrimidine (DAHP; 5 mM), were not significantly different from control values. When HD11 macrophages were cocultured with lymphoblastoid tumor targets, RECC-CU60 (T cell) or LSCC-RP9 (B cell), adding LPS (1 microgram/ml), tumor cell mitochondrial activity was significantly suppressed. In the generator macrophages, complex I was more suppressed than complex II, whereas in lymphoid targets no such difference was observed. These results indicate that .NO inhibits complex I and II mitochondrial activity but that differential targeting can occur among chicken leukocyte populations.

Animals↗
PubMed1994

2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTP cyclohydrolase I, suppresses nitric oxide production by chicken macrophages.

Biosynthesis of nitric oxide (.NO) from L-arginine by nitric oxide synthase (NOS) represents a major cytotoxic effector function of macrophages. It has been shown that most mammalian NOS requires tetrahydrobiopterin (BH4) as a cofactor and that inhibition of BH4 synthesis results in suppressed .NO production. Chicken L-arginine metabolism differs from that of mammals in that chickens cannot synthesize L-arginine de novo. Therefore, it is important to examine whether chicken macrophage .NO synthesis is also BH4-dependent. 2,4-diamino-6-hydroxypyrimidine (DAHP), a specific inhibitor for GTP cyclohydrolase I (GTP-CH; EC 3.5.4.16), the rate-limiting enzyme in de novo pterin synthesis, was used to block synthesis of BH4. Both chicken peritoneal macrophages (PECs) and the avian MC29 virus-transformed macrophage cell line, HD11, exhibited a dose-dependent reduction in .NO production (measured as nitrite accumulation) relative to DAHP concentration. Authentic BH4 and a substrate for pterin salvage pathway of BH4 synthesis, sepiapterin, were both capable of restoring the production of .NO in DAHP-treated PECs and HD11 macrophages. These results suggest that chicken macrophages require active synthesis of BH4 to produce .NO and that chemicals interfering with BH4 synthesis may result in suppressed .NO production and, hence, .NO-mediated immune function.

Animals↗
PubMed1994

Effect of dietary vitamin E and selenium deficiency on chicken splenocyte proliferation and cell surface marker expression.

Beginning at hatching, chicks were fed a Basal diet, without vitamin E or selenium (Se) or the same diet supplemented with vitamin E (100 IU/kg) and Se (0.2 ppm). The effect of these treatments on the expression of cell surface markers (CT-1a, CD3, CD4, CD8, sIgs, and Ia) defining specific thymocyte and peripheral blood leukocyte (PBL) subpopulations were examined using flow cytometric analyses. In parallel studies the effect of the dietary deficiencies on splenocyte proliferative responses to ConA or PHA stimulation was examined. The mean expression of CD3 and CT-1a per cell was increased while CD8 and CD4 expression was decreased on thymocytes from chicks fed the Basal diet. The proportion of double negative (CD4-, CD8-) thymocytes and single positive CD8+ thymocytes was significantly decreased while single positive CD4+ and double positive (CD4+, CD8+) thymocytes were significantly increased by the dietary vitamin E and Se deficiencies. The dietary deficiencies resulted in a decreased proportion of peripheral T cells and specifically decreased the number of CD4+ PBL. The proliferative response to both ConA and PHA was impaired by the vitamin E and Se dietary deficiencies. The proliferative response could be fully reconstituted but only after vitamin E and Se supplementation for periods longer than 1 week. Plasma SeGSHpx and alpha-tocopherol levels paralleled the mitogen responsiveness observed. These results support the conclusion that vitamin E and Se deficiencies may affect both the maturation of specific lymphocyte subpopulations and the functional and proliferative capabilities of the peripheral lymphocytes.

Animals↗
PubMed1994

Profiles of chicken macrophage effector functions.

In contrast to the mammalian system, avian species lack the so-called "resident" or "harvestable" macrophage population in the abdominal exudate. However, macrophages can be recruited into the chicken's abdominal cavity (presumably from the blood monocyte pool) if an inflammatory agent such as Sephadex is injected. The kinetics of inflammatory cell recruitment in terms of time, cell type, and state of activation to perform a particular effector function is currently an active area of research. This report will provide information on several chicken macrophage effector functions, including in vivo chemotaxis, phagocytosis, bacterial uptake and killing, biosynthesis of nitric oxide and various enzymes, and monokines such as interleukin-1 and granulocyte colony-stimulating factor.

Acid Phosphatase↗
PubMed1994

Environment-immune interactions.

The need for effective immune function for the maintenance of health has been clearly established in both agriculturally significant animal species and humans. Intensive agricultural practices present production species with numerous disease challenges during the rearing period. Environmental factors represent a ubiquitous, yet frequently manageable, category of immunomodulators that can influence immune performance and ultimately disease susceptibility or resistance. However, strategies for assessing overall immune potential have not been widely implemented for agricultural species. This is in contrast to the use of immune evaluation for human health considerations. Immune assessment relative to environmental-immune interactions can produce benefits in two areas. First, the efficiency of the production operation can be enhanced. Second, the welfare of the animals during the production cycle can be optimized. This paper presents an overview of environmental factors known to influence the immune function of poultry and the opportunities to manage environmental factors to benefit the health of the animals. In addition, the paper discusses the status of immunological assessment for humans and laboratory animals and proposes potential immune assessment panels that could serve as a tool to optimize the environmental management of poultry populations.

Animal Husbandry↗
PubMed1993

Avian macrophages: contribution to cellular microenvironment and changes in effector functions following activation.

The capacity of macrophages to generate metabolites and monokines having effector and regulatory functions can result in a major impact on their cellular microenvironment. Macrophage products synthesized in response to bacterial lipopolysaccharide stimulation include reactive oxygen and nitrogen intermediates as well as tumor necrosis factor (TNF). These secreted products of macrophages exhibit bioactivity either locally or systemically. Although the mechanism of action of avian monokines such as TNF-like factor may be similar to their mammalian counterparts, chicken TNF seems to lyse cells of chicken origin and not of mammalian origin. Furthermore, the generation and activity of products such as TNF is directly influenced by environmental stressors such as heat and toxins.

Animals↗
PubMed1992

Direct measurement of nitric oxide in headspace gas produced by a chicken macrophage cell line in a closed culture system.

A simple and rapid method was applied for direct measurement of nitric oxide (NO) gas produced by cultured macrophages using a modified chemiluminescence detector, the thermal energy analyzer (TEA). HD11 chicken macrophages (1-3 x 10(6)/ml) were cultured on microcarrier beads (100 mg/ml) in 140 ml air-tight glass jars (5 ml cell suspension per jar) containing 0.5 micrograms/ml of LPS and different concentrations of L-arginine. Headspace gas was sampled at 24 hours of culture via a rubber septum and directly injected into a TEA with a liquid nitrogen trap set at -130 to -140 degrees C. The concentration of NO in the gas sample was quantified using a standard gas mixture of NO (2 microliters/L) in nitrogen. Gas samples from L-arginine-supplemented cultures contained NO (0.028-0.066 pl/microliter), whereas NO was not detected in samples from controls. These results suggest that chicken macrophages synthesize NO gas in a dose-dependent manner relative to L-arginine concentration.

Animals↗
PubMed1992

Macrophage antimicrobial functions in a chicken MHC chromosome dosage model.

Macrophages respond to certain inflammatory signals with a marked increase in respiratory burst and the production of reactive oxygen intermediates; these metabolites play an essential role in the destruction of invading microorganisms. In this study, macrophage antibacterial inflammatory responses were compared among chickens having two (disomic), three (trisomic), or four (tetrasomic) copies of the major histocompatibility complex (MHC)-encoding microchromosome (B15 haplotype). Phorbol myristate acetate (PMA)-stimulated superoxide anion (O2-) production by cross-linked dextran (Sephadex)-elicited peritoneal macrophages was measured at early (4 h), intermediate (24 h), and late (42 h) stages of the inflammatory response using ferrocytochrome c reduction. Significantly elevated O2- production was observed for trisomic versus disomic macrophages during both early and intermediate stages of the inflammatory response. Late in the response, tetrasomic macrophages produced a significantly higher level of O2- than disomic cells. When PMA was used to trigger hydrogen peroxide (H2O2) production, no significant genotype difference was found for any stage of the inflammatory response. Phagocytosis of heat-killed Salmonella enteritidis by macrophages differed among the three genotypes: trisomic macrophages were superior to disomic cells during early inflammation, no genotypic difference was observed at the intermediate stage, and disomic cells had greater phagocytic capacity than aneuploid macrophages late in the response. Likewise, when S. enteritidis was cultured with macrophages to induce oxygen intermediate secretion, H2O2 production followed a kinetic pattern among the genotypes similar to that observed for bacterial phagocytosis. Endogenous superoxide dismutase (SOD), catalase, and glutathione peroxidase (GP) activities were determined for the macrophages during intermediate and late inflammatory stages. Tetrasomic macrophages had reduced SOD activity at the late stage, no significant difference was observed in catalase activity among genotypes at either time point, and trisomic macrophages had enhanced GP activity compared to disomic cells at both time points. These results indicate that differences in MHC gene dosage are associated with differences in chicken macrophage activation for the acquisition of selected antibacterial functions.

Aneuploidy↗
PubMed1992

Distribution and inducibility of a P450I activity in cellular components of the avian immune system.

The level of expression of the cytochrome P450 system in an immune tissue could influence the sensitivity of that immune tissue to damage by xenobiotics. The capacity of immune organs and their cellular components for P450I-catalyzed metabolism was assayed in the 4-week-old chicken using the P450I-specific ethoxyresorufin-O-deethylase (EROD) assay and the P450I-inducer, 3,4,3',4'-tetrachlorobiphenyl (TCB). After induction by TCB, EROD was detectable in microsomes from whole thymus, bursa and in peritoneal exudate cells (containing primarily macrophages) at levels of 28.3, 7.2 and 1.3 pmol/mg microsomal protein/min, respectively; the level in control liver was 89.9 pmol/mg microsomal protein/min. No activity was detected in these immune tissues without induction. The P450I specific in vitro inhibitor, alpha-naphthoflavone (NF) inhibited the TCB-induced liver and immune tissue EROD by 50% at concentrations in the range of 0.07-0.1 microM. The cellular distribution of EROD in the bursa and thymus was studied in lymphocytes and supporting tissue cells after their separation by density gradient centrifugation. Much higher TCB-induced EROD was detected in immune tissue supporting cells than in lymphocytes, particularly in the thymus. The P450I in the supporting tissue of the bursa and thymus at 1 week post-hatch was also measured after eradication of the lymphocytes in both immune tissues by in ovo administration of CP. TCB-induced EROD was 12-fold higher in the lymphocyte-depleted thymus than in normal thymus, with a less marked but similar pattern in the bursa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗