Biomedical subjects

K Krzystyniak

Publications and source records attributed to K Krzystyniak.

At least 37 records · Page 2Linked to original sources

PubMed1992

Combined effects of selected insecticides on humoral immune response in mice.

Biological effects data with single insecticides are far more abundant than with mixtures. These data cannot be used directly to predict the effects of insecticide mixtures. Three insecticides of different chemical classes: organochlorine; dieldrin, organophosphate; malathion, and carbamate; carbofuran, previously evaluated for their immunotoxic potential, were selected for studies of combined acute exposure in C57B1/6 inbred mice. The humoral response to sheep red blood cells (SRBC) and the functional activities of peritoneal macrophages, such as phagocytosis of fluorescent beads and presentation of a single protein antigen, avidin, were examined after in vivo exposure of mice to different combinations of the selected pesticides and compared with the vehicle controls. Regarding exposure to single substances, the data confirmed the immunosuppressive potential of dieldrin and carbofuran and the immunopotentiating effect of malathion. Following the acute concomitant exposure to dieldrin/carbofuran mixture, however, values for the parameters of antigen presentation, primary IgM antibody response to SRBC antigen, and macrophage phagocytosis, returned to control or above-control values, indicating a lack of any synergistic or additive effects of the chemicals on the immune response. Thus, it was concluded the dieldrin/carbofuran mixture had an antagonistic effect on the humoral response to SRBC and the macrophage phagocytic activity, in comparison with the action of administration of each of the insecticides alone.

Animals↗

PubMed1992

Limited immunotoxic potential of technical formulation of the herbicide atrazine (AAtrex) in mice.

Immunotoxicity of the technical atrazine formulation, AAtrex, was examined in C57Bl/6 female mice following a sublethal exposure to equivalent 1/2-1.64 LD50 doses of the herbicide. Animal weight was not affected by the herbicide exposure. No dose-related changes could be concluded for fluctuations in organ weight, changes in the spleen cell number and cell viability. Furthermore, cytofluorometric studies showed no significant changes in the frequency of L3T4-positive and Lyt-2-positive T-cells. Functional in vitro assays of mitogen activation showed no marked effects of AAtrex exposure on lymphocyte stimulation by lipopolysaccharide (LPS), phytohemagglutinin (PHA) and concanavalin A (Con-A). In addition, sublethal exposure to AAtrex did not affect interleukin-2 (IL-2) production by splenic cells. Furthermore, no dose-related effect could be concluded from a transient suppression of a primary humoral IgM response to sheep erythrocytes (SRBC) as well as from a transient inhibition of a specific T-cell response to alloantigens in mixed lymphocyte reaction (MLR). Exposure to equiv. 1/2-1/16 LD50 doses augmented phagocytic activity of peritoneal macrophages, without any visible AAtrex dose-related effect. Normal humoral and cellular responses were restored at 14-40 days after the herbicide exposure. Overall, transient and reversible immunosuppression of humoral-mediated and cell-mediated responses and activated macrophage phagocytic activity could not be attributed to the direct chemical-related effect of sublethal exposure to AAtrex.

Animals↗

PubMed1992

Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine popliteal lymph node (PLN) test.

Time-related and dose-related popliteal lymph node (PLN) enlargement and lymphocyte subset alterations owing to subcutaneous (s.c.) injection of streptozotocin (STZ) into the foot pad were determined in (C57BL/6 x DBA/2)F1 [B6D2F1] mice. Early cell activation and time-related changes in T and B lymphocyte subsets were monitored during the onset of STZ-induced lymphoproliferative reaction by flow cytometry and immunophenotyping of lymphocyte subsets stained with a panel of monoclonal antibodies. Examination of cell size and chromatin decondensing for T and B cell subsets revealed differences in their activation profiles during the early phase of STZ-induced lymph node enlargement. The kinetics of the reaction showed initial activation and proliferation of CD4+ cells associated with accumulation of CD8+ and B cells. Subsequently CD8+ cells were activated and proliferated, but there was no evidence of early or late B cell activation as shown by the lack of increase in cell size or nuclear decondensation and the low and transient synthesis of immunoglobulins. The activation characteristics for CD4+ and CD8+ cell subsets in STZ-induced node enlargement were found to be analogous with T cell activation in acute allogeneic graft-versus-host (GVH) reaction in which the F1 recipient differed from the parent at both class I and II MHC loci. Our data support a central role for T cell activation in the induction of STZ-related PLN enlargement and suggest that recirculatory host B cells can play a major role in early node enlargement.

Animals↗

PubMed1992

Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice.

Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N-nitrosodimethylamine (NDMA) was examined in CD-1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose-related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time-related, dose-related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low-hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD-1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite-inducing) doses of NDMA suppressed humoral and cellular immunity. The persistent immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA-related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression.

Animals↗

PubMed1992

Colloidal gold ultraimmunocytochemical localization of DNA and RNA adducts in rat hepatocytes.

The localization of DNA and RNA adducts was studied at the ultrastructural level using antibodies directed against O6-methylguanine (O6-metG) and the protein A-gold technique. Primary rat hepatocyte cultures were exposed for 2 h to 5 mM N-nitrosodimethylamine (NDMA). In NDMA-treated cells, the O6-metG-induced immunoreactive sites do not appear at random but seem to be concentrated in the nucleus, and in the cytoplasm, in areas rich in rough endoplasmic reticulum (RER) elements. Mitochondria were not significantly labelled. Untreated control preparations showed no specific immunogold labelling. After RNase digestion of ultrathin sections obtained from cells exposed to NDMA and subsequent immunogold labelling, most of the immunolabelling in the cytoplasm had disappeared, and that over the nucleus had only been slightly reduced, as compared to undigested specimens from NDMA-treated cultures. After similar digestion with DNase, a strong reduction of the labelling of the nucleus was observed, but labelling of the cytoplasm was practically unaffected by this enzymatic treatment, as compared to what was observed in undigested preparations of NDMA-treated hepatocytes. The results provide evidence of preferential formation of O6-metG at the DNA and RNA levels, in the nucleus and cytoplasm RER, respectively. Furthermore, this study demonstrates the applicability of the high-resolution protein A-gold technique for ultrastructural detection of nucleic acid adducts in NDMA-treated hepatocytes using affinity-purified anti-O6-metG polyclonal antibodies.

Animals↗

PubMed1992

Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2 incompatible F1 mouse hybrids.

Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ-induced PLN response in mice. The GVH reaction was induced locally by sc injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte subsets were monitored during the onset of the GVH reaction by flow cytometry and immunophenotyping. Examination of cell size and chromatin decondensing for T- and B-cell subsets showed differences in activation profile during the early phase of the GVH reaction. The present study provides direct evidence for early in vivo activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T-cell activation in the induction of a GVH reaction and suggest that recirculatory host B-cells can play an important role in early GVH node enlargement. Overall, our comparative analysis supports the concept of polyclonal T-cell activation for both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced lymphoproliferation leading to autoimmune reactions is a challenging issue. A number of drugs and chemicals have been tested in the PLNA assay for lymphoproliferative potential. We previously reported the activation and proliferation of T-cell subsets following STZ injection into murine footpads. The STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell subsets were postulated to be similar to those of an acute allogeneic GVHR. In the present study, a cytometric analysis of T- and B-cell subsets in PLNs was performed during an acute allogeneic GVHR, for comparison purposes. Such a reaction results in a massive node enlargement five to ten times that seen after stimulation with conventional antigens. Acute GVHR is believed to be a direct consequence of the high frequency of alloreactive donor T-cells inducing a massive proliferation of B-cells, almost exclusively of host origin, in GVHR nodes. It is now widely accepted that donor T-cells activated as the result of exposure to foreign MHC antigens in the recipient, secrete various cytokines which assist the host B-cells and bypass the normal B-T cell cooperation. Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model, requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Evaluation of the immunomodulatory potential of diethyl dithiocarbamate derivatives.

The cytotoxicity, immunotoxicity and immunomodulatory potential of four dithiocarbamate derivatives were assessed and compared with the effects of Immuthiol (diethyl dithiocarbamate, DE-DTC) in mice. Cellular stimulation and cell viability were examined after in vitro exposure of spleen lymphocytes to selected DTC analogues: N-methyl-D-glucamine dithiocarbamate (NMG-DTC), dimethyl dithiocarbamate (DM-DTC), dibuthyl dithiocarbamate (DB-DTC) and diisobuthyl dithiocarbamate (DIB-DTC). Lymphocyte activation by plant and bacterial mitogens: concanavalin A (Con A), phytohaemagglutinin (PHA), lipopolysaccharide (LPS) and allogeneic stimulation of cells in mixed lymphocyte reaction (MLR) were examined in vitro in the presence of 10(-4)-10(-9) g/ml DE-DTC and other selected DTC derivatives. No direct in vitro lymphoproliferative activity of DTC derivatives was observed, although a relatively stronger cytotoxicity with DE-DTC and DM-DTC was noted. In addition, the in vivo effects of DTC derivatives were examined by cytofluorometric profile of splenic and bone marrow cells as well as in mitogenic and allogenic responses, after i.v. exposures of animals to two subsequent (25 mg/kg b.w.) doses of the chemical. Less cytotoxic DIB-DTC, NMG-DTC and DB-DTC expressed weak in vivo immunostimulatory potential when compared with the effect of DE-DTC, whereas the effects of DM-DTC on alloantigenic and mitogenic lymphocyte stimulation were comparable with the known effects of DE-DTC. Cytofluorometric studies showed that the number of cytotoxic/suppressor T-cells (Ts) and helper T-cells (Th) in the cell was increased by DE-DTC and NMG-DTC only. In addition, DM-DTC appeared to affect the Ts/Th ratio. DE-DTC did not affect the B-cell subpopulation, whereas other derivatives induced marked modifications of the pre-B-cell subpopulations in bone marrow. Our data suggest that in vivo the immunostimulatory effect of DM-DTC could be accompanied with major changes in bone marrow B-cell frequency and alteration of spleen Ts/Th ratio.

Adjuvants, Immunologic↗

PubMed1989

The response of the pulmonary surfactant-associated alkaline phosphatase following acute cadmium chloride inhalation.

In order to identify sensitive and specific biochemical indicators of pulmonary damages caused by industrial contaminants, male Long-Evans rats were exposed to a cadmium chloride (CdCl2) aerosol (5 mg Cd/m3; MMAD = 1.4 microns; SDg = 1.8) for 1 hr. The rats were sacrificed at 1, 4, 8, and 16 days after treatment. The response of the pulmonary surfactant (SF) system, which prevents alveolar collapse during expiration by lowering the surface tension at the air-liquid interface, was of particular interest. The effect of CdCl2 inhalation on the SF system was monitored by assaying the alkaline phosphatase (AKP) activity and phospholipid (PL) content in an enriched surface active SF fraction purified from bronchoalveolar lavages. The AKP activity of the SF fraction was markedly decreased (99%) on Day 1, indicating an inhibition of AKP by Cd. The PL content remained at control level while the total protein content was significantly increased (199%). On day 4, the high recovery of PL (207%) and AKP activities (639%) may reflect an increased secretion caused by Type II cell hyperplasia. By Day 8 these parameters returned to baseline levels. On Day 16 both the AKP activity and the PL content of the SF fraction were decreased significantly. Concurrently, the activities of the acid phosphatase and the B-N-acetylglucosaminidase followed, but to a lesser extent, the response of the AKP activity on Days 1 and 4. They differed from AKP, however, in that their activities remained significantly elevated on Day 8 and in that they returned to baseline levels on Day 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

PubMed1989

Cysteine-induced changes of low molecular sulfhydryl/disulfide ratio in rat lymphoid cells.

Changes in total protein and nonprotein sulfhydryl content, cell membrane sulfhydryls and mitogen response were examined after incubation of rat lymphoid cells with L-cysteine. Distribution of 35S L-cysteine within the metabolic pool of low molecular thiols and protein thiols was determined by quantitative analysis of metabolites of the oxidative taurine pathway, glutathione, mixed disulfides and protein-associated radioactivity. Significant, incubation time-dependent increase of [3H] thymidine, [3H] uridine and [14C] leucine incorporation was observed in cysteine-preincubated, PHA-stimulated lymph node cells. Subsequent inhibition of PHA-response of lymphocytes and a marked increase of intracellular content of free (reduced form) cysteine was observed as a result of constant supply of cysteine into cells from the incubation medium. Maintenance of [35S] L-cysteine, transported into thymocytes within 3 hours, mainly in -SH form, was dependent on the constant presence of cysteine in the medium and slightly dependent on its concentration (0.01-10 mM). Cysteine catabolites of the oxidative taurine pathway, i.e. taurine, cysteinesulfinic acid and cysteic acid, as well as glutathione, low molecular mixed disulfides, protein cysteine mixed disulfides and proteinincorporated cysteine increased proportionally to the time of cysteine uptake but not to the increasing amounts of intracellular free cysteine. These results support the hypothesis of changed-SH/SS equilibrium of low molecular thiols due to the presence of high amounts of free cysteine, reflecting cell metabolism and functions.

Animals↗

PubMed1988

Transient inhibition of mixed lymphocyte reactivity by dieldrin in mice.

Dieldrin, a non-aromatic organochlorinated pesticide, was shown to be a potent modulator of the immune system. We had earlier demonstrated that mice treated with a single sublethal dose of dieldrin showed an impaired antibody response and reduced viral restriction mediated by macrophages. These dieldrin-induced immunosuppressive effects were shown to be dose dependent, when administered by the oral or intraperitoneal (i.p.) route. This study was undertaken to investigate the effect of dieldrin on the T-cell immune response. Lymphoid cells from mice injected i.p. 7 days earlier with 36 mg/kg body weight (0.6 LD50) dieldrin were assessed for their ability to recognize a foreign antigen and to proliferate in a mixed lymphocyte reaction (MLR) at 4, 7, 14 and 24 days post-treatment. We have demonstrated a strong but transient inhibition of MLR at 7 days after pesticide exposure. This effect was reversible and could not be attributed to a direct cell cytotoxicity, nor to the modulation of the T-cell ratio in lymphoid organs. Since the mitogen response was not impaired at this time point, we suggest that T-cell ability to recognize a foreign antigen can be altered by dieldrin, but not the proliferative potential of the cells.

Animals↗

PubMed1988

Abrogation of graft-versus-host reaction by dieldrin in mice.

Sublethal exposure to the organochlorine pesticide, dieldrin, decreased the T-cell immune response in mice. Indeed, a transient inhibition of the mixed lymphocyte reactivity (MLR) was noted at 7 days after intraperitoneal exposure to 0.6 LD50 dieldrin. The present study was undertaken to further investigate the effects of dieldrin on the T-cell immune response, using the graft-versus-host reaction (GVHR) as a model, in order to assess T-cell subset efficiency. Lymphoid cells of A/J mice injected intraperitoneally 7 days earlier with 36 mg/kg body weight dieldrin were transferred into H-2-incompatible F1 hybrids. With this model, known to induce a marked GVHR, we have observed that dieldrin inhibited the potential of parental cells to induce a GVHR in hybrid mice. This effect could not be attributed to a direct cell cytotoxicity, nor to the modulation of major T-cell subsets as shown by thymic and peripheral T-cell subpopulation analysis. Collaboration processes between these cellular subsets seem to represent a potential site for the dieldrin-induced suppression.

Animals↗

PubMed1988

Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs.

In order to establish an animal model for assessing early and sensitive biochemical indicators of pulmonary damage, we studied the effects of inhaled CdCl2 (5 mg/m3.h; mass median aerodynamic diameter (MMAD) = 1.4 microns; SDg = 1.8) on the antioxidant defense and pulmonary surfactant systems of rat lungs. Rats were sacrificed 1, 4, 8, and 16 d after inhalation. Pulmonary edema (wet/dry weight) was observed on d 1. The total activities of the enzymes superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD) in the lung homogenates of the treated animals were significantly throughout the 16-d period. Glutathione reductase (GR) was increased on d 4 and after. The general increases of SOD, GR, and the lysosomal enzymes acid phosphatase and beta-N-acetylglucosaminidase could be attributed to changes in the cellularity of the lung tissue. The significant increase in the specific activity of G6PD on d 4 suggested enzyme stimulation. Concurrently, the response of the surfactant system was measured by assaying the alkaline phosphatase (AKP) and the phospholipid content in the homogenates and in the cell-free bronchoalveolar lavage (BAL) fluids. The AKP activity in the homogenates decreased by 30%, while no activity was detected in the BAL on d 1, suggesting an inhibition of AKP by Cd. The secretion of surfactant seemed altered at this early time: phospholipid in the BAL decreased by 44%, although it increased by 61% in the tissue. The high recovery of phospholipid (312%) in the BAL on d 4 and the important changes in the AKP activity in the BAL from d 4 to 16 may reflect alterations in the processing of the surfactant. The effect of Cd on AKP makes this enzyme a potential marker of the metal redistribution in the pulmonary alveolar region, which could be a useful tool in long-term studies.

Acetylglucosaminidase↗

PubMed1988

Virus-pesticide interactions with murine cellular immunity after sublethal exposure to dieldrin and aminocarb.

Interaction of two potential immunosuppressive factors, sublethal pesticide exposure and viral inhibition of lymphocyte mitogenesis, was examined in mixed lymphocyte reaction (MLR). Inbred (C57Bl/6 x A/J)F mice, semisusceptible to mouse hepatitis virus 3 (MHV3) infection were exposed to selected pesticides and subsequently infected with the MHV3 virus. The mortality of animals was examined as a function of pesticide exposure. Two pesticides were selected for further studies: the organochlorine pesticide dieldrin, which increased the cumulative mortality of animals, and the carbamate pesticide aminocarb, which did not affect the virus-induced cumulative mortality of animals. Spleen lymphocytes from dieldrin- and aminocarb-exposed C57Bl/6 mice (susceptible to MHV3 infection) were used as responder cells in one-way MLR. A marked immunosuppression of the MLR proliferative response was observed in the dieldrin group, whereas sublethal exposure to aminocarb did not affect the in vitro MLR response. The MLR cultures were subsequently infected in vitro with the MHV3 virus, which resulted in a time-dependent and virus dose-dependent inhibition of lymphocyte proliferation. However, no synergism was observed with the addition of either the MHV3 virus-induced inhibition of in vitro MLR lymphoproliferative response or dieldrin-related immunosuppression, since in vitro MHV3 infection of cells from dieldrin-exposed mice did not aggravate the dieldrin-related immunosuppression. In addition, no "hidden" aminocarb-related damage of the lymphoproliferative response was noted, as the kinetics of the virus-induced inhibition in the aminocarb group were analogous to the control. In conclusion, dieldrin-induced immunosuppression of the cellular immune response, rather than MHV3 virus-induced inhibition of lymphoproliferative activity itself, was the primary factor potentially responsible for the impaired cellular response. Furthermore, the data support the observation that cell-mediated immunity can be a potential target for the adverse effects of pesticide exposure.

Animals↗

PubMed1988

N-ethylmaleimide differentially affects adenosine and thymidine uptake by rat thymocytes.

The involvement of membrane sulfhydryl groups in the uptake of adenosine and thymidine was examined in rat thymocytes pretreated with 6,6'-dithiodinicotinic acid (CPDS) and N-ethylmaleimide (NEM). CPDS, which is known to react uniquely with external membrane sulfhydryls, under short incubation conditions, did not significantly affect the uptake of adenosine and thymidine. Formation of cAMP in nonstimulated and adenosine-stimulated cells was also unaltered by CPDS. However, inhibition of adenosine uptake by competitive inhibitor, dipyridamole, was significantly stronger when the cells were pretreated with CPDS. Preincubation of cells with NEM showed differential sensitivity of adenosine and thymidine uptake, depending on concentration of this sulfhydryl alkylating agent. The results suggest the involvement of NEM-accessible sulfhydryls in membrane transport of adenosine and thymidine. Dual effect of NEM on nucleoside transport may be related to the complexity of nucleoside carrier(s) or to the existence of different nucleoside carriers within thymocyte membranes. On the other hand, the easily accessible, external membrane -SH groups which can be blocked with CPDS, are not essential in thymocyte nucleoside transport but they appear to be situated at a site which interacts with the membrane transport system of nucleoside.

Adenosine↗

PubMed1987

Immunosuppression in mice after inhalation of cadmium aerosol.

Aerosol cadmium (CdCl2) exposure of female C57Bl/6 mice was performed to assess the in vivo effects of cadmium on the cellular and humoral immune responses of splenic lymphocytes. Primary cellular and humoral responses of lymphocytes were examined at 5-18 days after a single, 60 min exposure to 0.88 mg Cd/m3 (MMAD = 0.7 +/- 0.3 micron, sigma g = 3.43). Significant decrease of in vitro lymphoproliferative response to allogeneic antigens, LPS and PHA antigens, and inhibition of the primary IgM response to sheep erythrocytes were correlated with a marked decrease in spleen cell viability at 5-8 days after aerosol cadmium exposure. This type of cadmium-induced immunosuppression, which correlated with the direct cytotoxicity of effector cells, appeared to be different from the chronic, oral cadmium-induced suppression of the primary IgM response, in which acute cytotoxicity of the spleen cell population was not observed.

Administration, Inhalation↗

PubMed1987

Suppression of humoral immunity in inbred mice by dieldrin.

The effect of single, sublethal i.p. injection of dieldrin on the primary antibody response to thymodependent (sheep red blood cells, SRBC) and T-cell-independent (lipopolysaccharide, LPS) antigens were investigated in inbred C57Bl/6 mice. Time-course studies showed significant suppression of the anti-SRBC IgM and anti-LPS IgM response at 7-24 days and at 4-14 days, respectively, after exposure to 0.6 LD50 of dieldrin. The anti-SRBC IgG response was also suppressed by dieldrin exposure, however, maximal suppressory effect was found at 48 days after the pesticide exposure. Similar patterns of the dieldrin-induced suppression of the primary IgM response to the thymodependent and T-cell-independent antigens, in addition to the overall control of cytotoxicity of lymphoid cell populations, suggest rather dysfunction of cellular cooperation during the inductory phase of the immune humoral response.

Animals↗

PubMed1986

Suppression of MHV3 virus-activated macrophages by dieldrin.

Dieldrin (36 mg/kg body weight) administered intraperitoneally prolonged recovery from infection with mouse hepatitis virus 3 (MHV3) in the genetically-resistant A/J strain, affected the humoral anti-MHV3 IgG immune response, and inhibited the intrinsic antiviral activity of peritoneal macrophages upon in vitro rechallenge with the virus. Infection of untreated A/J animals and vehicle controls with MHV3 resulted in marked and reproducible activation of peritoneal macrophages, observed in vitro as resistance to MHV3-cytopathic effects 48 hr after rechallenge with the virus, whereas exposure to dieldrin resulted in apparent loss of the intrinsic capacity of cells to restrict replication of MHV3 and to protect them from cytolysis. In addition, in vitro treatment of MHV3 virus-activated macrophages with dieldrin, mitomycin C and X-irradiation, inhibited the intrinsic capacity of cells to restrict MHV3 replication. This mechanism of cellular restriction of the virus by MHV3-activated macrophages from the resistant A/J strain appeared to be one of the sensitive targets for the suppressive action of dieldrin on host resistance, as no major changes in macrophage cellular parameters were observed in in vitro studies of cell viability, adherence to plastic, and superoxide anion generation; the increased cell yield in the peritoneal exudates during MHV3 virus infection was not affected by dieldrin exposure; and the attachment and uptake of [3H]MHV3 by virus-activated macrophages was shown to be unchanged by dieldrin exposure.

Animals↗

PubMed1985

Increased susceptibility to mouse hepatitis virus 3 of peritoneal macrophages exposed to dieldrin.

Interaction of a single dose (36 mg/kg body wt) of the organochlorine pesticide dieldrin with mouse peritoneal macrophages was examined in C57Bl/6, (C57Bl/6 X A/J)F1, and A/J strains of different genetic resistance to mouse hepatitis virus 3 (MHV3) infection. In vivo studies showed increased susceptibility to MHV3 acute disease of C57Bl/6 and (C57Bl/6 X A/J)F1 animals challenged with the pesticide. Significant decrease of mean time of death in dieldrin-exposed, MHV3-infected susceptible C57Bl/6 mice was observed similarly upon po or ip administration of a single, sublethal dose of dieldrin. In addition, decrease of humoral response to the virus was quantified by determination of anti-MHV3 IgG antibodies in spleen cell supernatant fractions and in blood sera of dieldrin-exposed C57Bl/6 mice. A single dose of dieldrin did not alter the in vivo resistance of A/J animals to acute MHV3 disease. The resistant A/J mice, however, showed increased mortality upon two subsequent exposures to dieldrin followed by infection with high lethal doses of MHV3. Phagocytic activity, cell adherence capacity, and attachment and uptake of 3H-radiolabeled MHV3 by C57Bl/6 peritoneal macrophages were determined by in vitro studies. These affector activities of peritoneal macrophages were slightly decreased or unchanged in cells originating from animals exposed to the pesticide. However, the intrinsic activity of MHV3 restriction appeared to be affected in macrophages derived from dieldrin-treated animals: (i) peritoneal C57Bl/6 macrophages collected from the early phase of acute MHV3 disease contained increased MHV3 antigen and (ii) increased cytolysis was observed after in vitro MHV3 infection of macrophages originating from dieldrin-exposed C57Bl/6 mice.

Animals↗