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Biomedical subjects

A Zarkower

Publications and source records attributed to A Zarkower.

At least 19 recordsLinked to original sources

Age-related differences in subset composition and activation responses of intestinal intraepithelial and mesenteric lymph node lymphocytes from neonatal swine.

Interesting differences were found in the phenotypes and functional responses of intestinal intraepithelial lymphocytes (IEL) and mesenteric lymph node lymphocytes (MLN) from neonatal swine aged 15 to 47 days. IEL and MLN differed significantly in their proliferative responses to the mitogens concanavalin A (Con A) and phorbol ester with ionophore (TPA/ionomycin) and to the cytokine, interleukin 2 (IL-2). IEL did not proliferate well in response to Con A, yet they were able to initiate a high proliferative response to exogenous IL-2, suggesting previous activation. In addition, the IEL response to TPA/ionomycin was very low unless the concentration of ionomycin was increased. With increasing age of the animals, response of the IEL increased. This IEL developmental response pattern was associated with a significant age-related change in T cell phenotype from CD2-4-8- cells to CD2+4-8- cells. In contrast to IEL, proliferation of MLN to Con A and TPA at a lower ionomycin concentration was significant and not influenced by age. Unlike the IEL, MLN were unresponsive to exogenous IL-2. Similar to IEL, they produced very little IL-2 in response to Con A stimulation. Both lymphoid tissues contained 70% T cells and in the MLN more cells were CD4+ or CD4+8+ and fewer were CD4-8- compared to the IEL. These differences between IEL and MLN in neonatal swine may reflect differences not only in the state of cell activation related to the in vivo microenvironment, but also the nature of responsive cell types in each lymphoid tissue.

Age Factors↗

Increased thromboxane A2 synthesis by rat lung neutrophils during selenium deficiency.

Modulation of cellular hydroperoxide levels is considered one of the important physiological mechanisms for regulating the synthesis of prostaglandins (PGs) and leukotrienes (LTs) in mammalian cells. Both vitamin E and selenium (Se) have the potential to affect the concentration of peroxides and, thus, the biosynthesis of eicosanoids. To gain insight into some of the molecular mechanisms underlying the regulation of the arachidonic acid cascade by vitamin E and Se, we have investigated the influence of altered vitamin E and Se nutrition on the ability of polymorphonuclear leukocytes (PMNs) derived from endotoxin-challenged lung to secrete arachidonic acid metabolites. Selenium deficiency had no significant effect (p > 0.05) on lavage fluid levels of thromboxane (TX) B2, LTB4 or LTC4. Vitamin E deficiency, however, led to a significant increase in LTB4 recovered from lavage fluid while having no effect on TXB2. In contrast, Se deficiency, although producing no discernible effects on the production of LTB4, resulted in a significant increase in the release of TXB2 by PMNs. An increase in TXB2 release was seen in both in vitro-stimulated and nonstimulated PMNs. Vitamin E deficiency appeared to induce an enhancement of LTB4 release by PMNs but the increase was not statistically significant. No detectable levels of LTC4 were found in PMN cultures stimulated with either zymosan or A23187. Thus, these studies indicate that deficiencies of either Se or vitamin E lead to alterations in the metabolism of arachidonic acid in the lung.

Animals↗

Effects of inadequate vitamin E and/or selenium nutrition on the release of arachidonic acid metabolites in rat alveolar macrophages.

Effects of vitamin E and/or selenium (Se) deficiency on the secretion of arachidonic acid metabolites by zymosan-stimulated pulmonary alveolar macrophages (AM) were examined using cells from male Long-Evans hooded rats fed torula-yeast based diets with or without the supplementation of vitamin E (150 IU/kg) or Se (0.5 mg/kg). Alveolar macrophages obtained by lavage were purified by adherence and cultured for 4 h in Hank's balanced salt solution containing bovine serum albumin (0.1%) and zymosan (300 micrograms/ml). The arachidonic acid metabolites present in the culture supernatant were measured by radioimmunoassay. Altered vitamin E and Se nutrition had no effect on the number of cells or cell types recovered from the pulmonary airways. Alveolar macrophages derived from animals fed on diets deficient in vitamin E or Se or both nutrients secreted higher levels of prostaglandin E2 and thromboxane B2. Levels of both 5-hydroxyeicosatetraenoic acid and leukotriene B4 were significantly increased only in the group fed the diet adequate in Se but deficient in vitamin E. Our data suggest that vitamin E and Se might play an important role to control the levels of several physiologically and pathologically important arachidonic acid metabolites.

Animals↗

Comparison of dot immunobinding assay, enzyme-linked immunosorbent assay and immunodiffusion for serodiagnosis of paratuberculosis.

A rapid, simple and inexpensive dot immunobinding assay (DIA) was evaluated for the serodiagnosis of paratuberculosis in cattle. The assay was performed on nitrocellulose strips which were dotted with purified protoplasmic antigen of Mycobacterium paratuberculosis. After incubation with test serum samples, the bound antibodies were detected using an enzyme-amplified immunostaining procedure. The efficacy of DIA as a screening test for paratuberculosis was compared to that of an enzyme-linked immunosorbent assay (ELISA), a modified agar gel immunodiffusion (mAGID) test, and an AGID test using 329 serum samples from cattle which were examined for M. paratuberculosis infection by a sensitive fecal culture technique. The DIA and ELISA had comparable results and both of the enzyme immunoassays had higher sensitivity than tests based on AGID. The sensitivity of all four tests was influenced by the intensity of fecal bacterial shedding. Preabsorption of sera with Mycobacterium phlei increased the sensitivity of both enzyme immunoassays. the specificity but reduced the sensitivity of both enzyme immunoassays.

Animals↗

Porcine effector mechanisms: antibody-dependent cell-mediated cytotoxicity of pseudorabies-infected target cells.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against pseudorabies virus (PRV)-infected cells was determined in neonatal porcine pulmonary washout cells and in partially purified blood-derived leukocytes. The ADCC assays were performed at approximately 1, 2, 3 and 11 days after birth. It was found that pulmonary-derived cells had a low level of cytolytic activity against the PRV-infected target cells at about 1 day of age. This activity increased sharply during the next 2 days of age, but declined somewhat by 11 days of age. The increase in ADCC activity paralleled closely the increase in the relative and absolute numbers of macrophages in the alveolar washout fluids. ADCC activity was high at all times in blood-derived neutrophils, and present in blood-derived lymphocytes, but at a lower level of activity.

Animals↗

Comparative humoral responses to Escherichia coli and sheep red blood cell antigens introduced via the respiratory tract.

The numbers of specific antibody-forming cells (AFC) in mediastinal lymph nodes (MLN) and spleen were determined in Balb/cByJ mice following inhalation or intratracheal (IT) injection of acetone-dried E. coli or its lipopolysaccharide (LPS). These responses were compared with those obtained using sheep red blood cells (SRBC), an antigen previously used in studies of pulmonary immunity. Inhalation of aerosolized E. coli for as little as 2 min produced significant numbers of AFC in both MLN and spleen, while equivalent administrations of SRBC produced few AFC at either site. Similarly, IT instillations of E. coli resulted in recovery of AFC from MLN and spleen, while IT SRBC produced AFC in MLN but few splenic AFC. IT installations of radiolabeled SRBC and E. coli were used to examine antigen dissemination, and no differences were found in the amounts of radiolabel recovered from various tissues following instillation of either antigen. Experiments using endotoxin resistant mice, and using administrations of LPS in combination with SRBC, were unable to demonstrate alterations in AFC production due to effects of LPS. It was found, however, that inhaled or IT injected E. coli or LPS produced greater pulmonary inflammation than did similar administrations of SRBC, and this may be at least partly responsible for the enhanced induction of systemic immunization.

Administration, Inhalation↗

Relationship of silica and bacillus Calmette-Guerin exposures to humoral and cellular immune functions.

The consequences of silica preexposures were studied on subsequent bacillus Calmette-Guerin (BCG) pulmonary infections. Silica had a variable effect on colonization by BCG depending on organ and number of BCG treatments. Silica preexposures resulted in increased numbers of free alveolar cells subsequent to BCG infections, with an initially rapid increase of neutrophils. Both silica and two BCG treatments were capable of decreasing the animals' splenic response to stimulations with Escherichia coli aerosols, and BCG greatly enhanced antibody-dependent cell-mediated cytotoxicity in silica preexposed mice. 5'-Nucleotidase activity was depressed by both silica and BCG in pulmonary washout cells indicating that inhalation of these substances may have a stimulating effect on the alveolar macrophages.

Animal Diseases↗

Comparative pathological aspects of chronic olivine and silica inhalation in mice.

A comparative study was done in mice on the effects of silica and olivine inhalation. The exposure periods in the dust chambers were for periods of 150, 300, and 570 days, with the longest time period covering a large portion of the predicted life span of the Balb/c mouse. Detailed necropsies including histology were done at the end of the exposures and at 30 and 150 days following removal of animals from the 150- and 300-day dust exposures. The results indicate that silica causes considerably more tissue damage in lungs and mediastinal lymph nodes, leading to granulomas.

Animals↗

The effects of ozone inhalation on the immunological response of selenium- and vitamin E-deprived rats.

Deficiencies in vitamin E (E) or Se result in immune alterations, possibly due to reduction of antioxidant activity. Such reductions might greatly compromise the ability of the immune system to deal with additional oxidant stress, as encountered during exposure to air pollutants such as ozone (O3). To study possible interactions of these oxidative stresses on immune function, male Long-Evans hooded rats were maintained 5 weeks on torula yeast-based diets, with or without the addition of E or Se. Each dietary group was subdivided into O3-exposed and nonexposed groups. Two different regimens of O3 exposure were used: continuous (1.0 ppm, 8 hr/day for 7 days) or intermittent (2.0 ppm, 8 hr/day for 4 days, 2-4 days in ambient air followed by 1 day of exposure prior to sacrifice). Exposure to O3 in either regimen resulted in increased numbers of cells recovered by pulmonary lavage. With continuous exposure this increase was due to macrophage influx and, with intermittent exposure, due to influx of both macrophages and neutrophils. Combined deficiency of E and Se led to an enhanced ability of spleen and lung cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCMC). In animals deficient in E, but not Se, O3 exposure depressed spleen cell ADCMC. Deficiencies of either E or Se also depressed lymphocyte response to mitogens. Although intermittent exposure to O3 caused no changes in mitogen response, in animals exposed continuously to O3 there was a significant enhancement of this response.

Animals↗

Antioxidant effects on cell-mediated immunity.

Experiments were performed to determine the effects of dietary selenium and/or vitamin E deficiency on cell-mediated cytotoxicity in the mouse. Natural killer cell-mediated cytotoxicity (NKCC) was depressed after 8 wk on diets deficient in selenium and/or vitamin E. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) was not affected by 8 wk of dietary deficiency of selenium and/or vitamin E. T-lymphocyte-mediated cytotoxicity (TCMC) was found to be depressed by combined selenium-vitamin E deficiency after 7 weeks on diets.

Animals↗

Effects of prolonged inhalation of silica and olivine dusts on immune functions in the mouse.

Immunologic responses were determined in Balb/c mice following intermittent silica or olivine inhalations for 150, 300, or 570 days. Animals dust-exposed for 570 days were tested immediately postexposure, while those exposed for 150 or 300 days were tested immediately or were rested for 30 or 150 days as a measure of possible recovery from effects of the dust inhalations. Silica inhalation suppressed the number of specific plaque-forming cells (PFC) in the spleen produced in response to aerosolized Escherichia coli bacteria. When tested after 570 days, silica inhalation also reduced the ability of alveolar macrophages to phagocytize Staphylococcus aureus in vitro. Olivine inhalation also suppressed splenic PFCs and alveolar macrophage phagocytosis, but to a lesser degree than silica. In animals tested after 570 days of dust exposure, it was determined that the ability to lyse allogeneic tumor cells in vitro was impaired by olivine slightly more than by silica, while antibody-dependent cell-mediated cytotoxic and mitogenic responses by splenic lymphocytes were unchanged by inhalation of either dust. The effects of increased exposure periods, and of recovery periods after exposure, were confounded by age-related immunologic changes which were present after the longer exposures.

Aerosols↗

Effects of vitamin E and selenium deficiencies on rat immune function.

The effects of dietary restriction of vitamin E and selenium were studied in male Long-Evans hooded rats. Weanling animals were maintained for 5-6 weeks on torula yeast-based diets, with or without the addition of vitamin E (150 IU/kg) or selenium (0.5 mg/kg), to form the following dietary groups: +E, +Se; +E, -Se; -E, +Se; -E, -Se, and a fifth group pair-fed with the -E, -Se group. This latter group exhibited a decreased rate of growth similar to the -E, -Se group. Lymphocyte blastogenesis in response to mitogens was decreased in animals fed the diets deficient in either vitamin E or selenium, and also in the pair-fed group. Very marked suppression of mitogen responses was seen in the doubly deficient group, as well as a greater loss of viability during culture. Spleen cell-mediated antibody-dependent lysis of chicken erythrocytes was increased in the doubly deficient group, although this difference could be abolished by the addition of catalase, but not indomethacin, to the culture medium. Dietary deficiency of vitamin E and selenium had no discernible effects on alveolar macrophage function, as measured by cell-mediated antibody-dependent cytolysis, killing of Staphylococcus aureus or regulation of T-lymphocyte blastogenesis.

Animals↗

The effects of silica and fly ash dust inhalation on alveolar macrophage effector cell function.

Inhalation of silica was found to cause significant enhancement of alveolar macrophage antibody-dependent cell-mediated cytotoxicity (ADCC) after 14, 42, and 70 days of exposure, while similar treatment using fly ash resulted in significant suppression of ADCC after 42 days of exposure. Both silica and fly ash inhalation depressed the ability of alveolar macrophages from BCG-primed and BCG-rechallenged animals to mediate tumor cell lysis. Fly ash exposure also significantly suppressed the ability of BCG-activated macrophages to lyse target cells by the ADCC mechanism.

Adjuvants, Immunologic↗