Search PubMed⌕ Search

Biomedical subjects

J G Vos

Publications and source records attributed to J G Vos.

At least 73 records · Page 4Linked to original sources
PubMed1993

Immunotoxic effects of the color additive caramel color III: immune function studies in rats.

Administration of the color additive caramel color III (AC) may cause a reduction in total white blood cell counts in rats due to reduced lymphocyte counts. Beside lymphopenia, several other effects in rat have been described. The effects are caused by the imidazole derivative 2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) and occur in rats fed a diet low in vitamin B6. In the present paper, immune function studies on AC and THI with rats fed a diet low, but not deficient in vitamin B6 are presented and discussed. Rats were exposed to 0.4 or 4% AC or to 5.72 ppm THI in drinking water during and for 28 days prior to the start of immune function assays. Resistance to Trichinella spiralis was examined in an oral infection model and clearance of Listeria monocytogenes upon an intravenous infection was studied. In addition, natural cell-mediated cytotoxicity of splenic and nonadherent peritoneal cells and the antibody response to sheep red blood cells were studied. From the results it is concluded that exposure of rats to AC or THI influenced various immune function parameters. Thymus-dependent immunity was suppressed, while parameters of the nonspecific resistance were also affected, as shown by a decreased natural cell-mediated cytotoxicity in the spleen and an enhanced clearance of L. monocytogenes.

Animals↗
PubMed1993

The role of oxidative metabolism in hexachlorobenzene-induced porphyria and thyroid hormone homeostasis: a comparison with pentachlorobenzene in a 13-week feeding study.

Hexachlorobenzene (HCB) induces a broad spectrum of effects including disturbances in the heme synthesis (porphyria) and in thyroid hormone homeostasis. For most of its effects, biotransformation of the parent compound seems to be a prerequisite. The present study was designed to assess the relevance of the oxidative metabolites in HCB-induced toxicity, with special attention to the role of the reactive tetrachlorobenzoquinone (TCBQ). To this end, toxicity and biotransformation of HCB were compared with those of pentachlorobenzene (PCB), since this chemical is oxidized to the same products as HCB, i.e., pentachlorophenol (PCP) and TCBQ. Female Wistar rats received diets containing different dose levels of HCB or PCB for 13 weeks, with or without cotreatment with triacetyloleandomycin (TAO), a selective inhibitor of cytochrome P450IIIA1/2. Rats treated with HCB (high dose) had significantly elevated levels of urinary porphyrins from the 4th week on and had a significant hepatic accumulation of porphyrins at the end of the study. Both urinary porphyrin excretion and hepatic porphyrin accumulation were greatly inhibited in rats receiving cotreatment with HCB and TAO. However, the inhibition of HCB-induced porphyria by TAO cannot be explained by a diminished formation of the highly reactive TCBQ, since rats treated with a high dose of PCB, which had a several fold higher urinary excretion of PCP and TCHQ compared to a high dose of HCB, did not develop porphyria. Instead, the present study points to the involvement of a putative reactive intermediate in the primary oxidative step in HCB-induced porphyria, since based on paired observations of individual rats, the degree of porphyria was correlated to a high degree with excretion of PCP, whereas correlation of porphyria with early excretion of TCHQ was much weaker. This finding fits well with the fact that the mechanisms of oxidation of HCB to PCP and PCB to PCP are different. Both HCB and PCB were oxidized to PCP and tetrachlorohydroquinone (TCHQ), the reduced analog of TCBQ. Cytochrome P450IIIA1/2 appears to be involved in the conversion of HCB and PCB, since cotreatment of TAO resulted in a strongly diminished urinary excretion of PCP and TCHQ. Treatment with HCB as well as PCB results in disturbances of retinoid and thyroid hormone homeostasis. These effects, which have also been reported after exposure to polychlorinated biphenyls, originate from interference of hydroxylated metabolites (notably PCP) with the plasma thyroxine transport protein, transthyretine, and since this metabolite is formed from both HCB and PCB, this results in the same toxicity for both compounds.

Animals↗
PubMed1993

Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 micrograms/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from "pale" to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 micrograms/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 micrograms/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.

Animals↗
PubMed1993

The cortical epithelium of the rat thymus after in vivo exposure to bis(tri-n-butyltin)oxide (TBTO). An (immuno)histological and ultrastructural study.

Bis(tri-n-butyltin)oxide (TBTO) induces cortical atrophy in the rat thymus. We studied the potential involvement of the cortical epithelium in TBTO-induced thymotoxicity by (immuno) histology and electron microscopy. Juvenile male Wistar rats were orally intubated once with either 30 or 90 mg/kg TBTO and sacrificed 4 or 10 days later. A dose-dependent thymic atrophy occurred. Anti-keratin labelling showed epithelial cell aggregation in some animals at 10 days after exposure to 90 mg/kg TBTO, when recovery of the thymus was apparent. At the ultrastructural level, a relative shift was observed from "pale" to darker epithelial cell subtypes at the 30 mg/kg dose level, both at day 4 and day 10 after intubation. This phenomenon was not observed after exposure to 90 mg/kg TBTO. Both the altered keratin distribution and the increased electron density of the epithelium probably represent non-specific phenomena. The present morphological observations support the concept that TBTO affects the thymus via its action on lymphoid cells rather than on the epithelial compartment.

Animals↗
PubMed1992

Abnormal thymus development and impaired function of the immune system in rats after prenatal exposure to aciclovir.

Aciclovir (synonym: acyclovir) causes abnormal thymus development in rats. After treatment on day 10 of gestation a weight reduction of the organ is obvious in 21-day-old fetuses which persists postnatally. Adult male rats exposed in utero to one or three injections of 100 mg aciclovir/kg body wt given to the dam on day 10 of pregnancy showed a reduction of the thymus weight to 333 +/- 158 mg and 276 +/- 61 mg (control: 428 +/- 92 mg; n = 10). Corresponding alterations were detectable in female offspring. Liver weight was also decreased and spleen weight (in relation to body wt) was significantly increased in the offspring after the three exposures. In a host resistance model with Trichinella spiralis the function of the immune system of rats prenatally exposed to aciclovir was examined. Six weeks postnatally 10-12 randomly selected male rat offspring of one control and two treatment groups (1 or 3 injections of 100 mg aciclovir/kg body wt on day 10 of gestation) were infected orally with 500 Trichinella spiralis muscle larvae. Before and several times after the infection blood was taken from a tail vein or obtained by decapitation for examination of the antibody titers (IgM, IgG, IgA, IgE) to antigens of T. spiralis. Six weeks after the infection the weight of relevant organs was determined and tongue preparations were used for T. spiralis muscle larvae counting. Aciclovir exposed animals showed a different immune response than control rats. IgM titers in both treatment groups were higher than in controls two weeks after the infection but not different by the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗
PubMed1992

Alterations in the cortical thymic epithelium of rats after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): an (immuno)histological study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces thymic atrophy in rats. The present study was initiated to provide (immuno)histological data on the mechanism of action. Juvenile male Wistar rats were orally intubated once with 50 or 150 micrograms/kg TCDD. They were euthanized 4 or 10 days thereafter, or were allowed to stay alive until Day 20 or 26. Growth retardation occurred rapidly in all TCDD-treated animals. Lethality was demonstrated within 20-21 days after administration. At Days 4 and 10 after intubation, thymic atrophy was shown by reduction of thymic weight and cortex/medulla ratio. Staining patterns for T-cell markers in the atrophic thymuses coincided with the reduction of cortical areas. There was no evidence indicating that the effects were indirectly caused by stress. TCDD-induced thymic atrophy persisted until Day 26 after administration. Immunohistochemical analysis revealed prominent changes in the cortical thymic epithelium at the 150-micrograms/kg dose level. First, in the cortex epithelial cell aggregates were observed both at Day 4 and at Day 10 after administration. Apparently, the architecture of the epithelium had changed in these animals. Second, at 10 days after administration epithelial cells were found with the simultaneous expression of markers that in the normal uninvoluted thymus only occur either in the subcapsular/medullary area or in the cortex. This phenotype points to an unusual stage of differentiation. We conclude that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Apparently, it disturbs the epithelial network and interfers with the differentiation of epithelial cells.

Animals↗
PubMed1992

Chemicals trophic for the thymus: risk for immunodeficiency and autoimmunity.

The thymus is considered as the privileged site of T-lymphocyte generation. The organ is extremely vulnerable to the toxic action of chemicals. The classical example is the "acute stress-induced involution" mediated by glucocorticoid steroid hormones from the adrenal cortex. Nowadays a number of substances have been identified that act in a differential way on the thymus. Examples presented are some organotin compounds acting on immature lymphoblasts in the outer cortex, glucocorticosteroids acting on small thymocytes in the cortex, 2,3,7,8-tetrachlorodibenzo-p-dioxin acting on epithelial cells in the cortex, and cyclosporin acting on dendritic cells and epithelium in the medulla. The mechanisms of toxicity include receptor binding (Ah, aryl hydrocarbon receptor; dioxin); the Ca(2+)-dependent activation of an endogenous endonuclease resulting in DNA fragmentation ("programmed cell death" or apoptosis; dioxin and glucocorticosteroids); and interference with cell proliferation (some organotin compounds). The consequences of toxicity can be a decrease in thymic output of newly-generated T-lymphocytes (i.e. generation of a new T-cell repertoire), or induction of autoimmune symptoms by the creation of unwanted repertoire. This latter phenomenon may be applicable to cyclosporin that under specified conditions can induce so-called syngeneic graft-vs-host disease. This survey presents a brief description of the function of the thymus and the various thymic cell populations involved. Thereafter the susceptibility to toxic insults and the mechanisms of toxicity are reviewed. Finally, the consequences of toxic action for the host defence system, and hence the health status, are considered.

Adrenal Cortex Hormones↗
PubMed1992

Effects of the colour additive caramel colour III on the immune system: a study with human volunteers.

Administration of the colour additive Caramel Colour III to rats has been associated with decreased numbers of lymphocytes and several other changes in the immune system, as well as in immune function parameters, specifically in animals fed a diet with a relatively low vitamin B6 content. The effects are caused by the imidazole derivative 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Caramel Colour III is commonly used in food products such as bakery products, soya-bean sauces, brown sauces, gravies, soup aromas, brown (dehydrated) soups, brown malt caramel blend for various applications, vinegars and beers, and effects in humans on dietary intake cannot be excluded. Elderly male volunteers with a marginal deficit in vitamin B6 were considered a relevant and potentially sensitive group to study possible effects of Caramel Colour III on blood lymphocyte numbers (total and within subsets) or on proliferative responses of lymphocytes to mitogenic stimulation. In addition, several other haematological parameters, as well as serum immunoglobulin levels and immunoglobulin production in vitro by pokeweed mitogen-stimulated mononuclear blood cells were studied. The results of this double-blind intervention study demonstrated that in a selected test group of apparently healthy elderly male volunteers with a biochemically marginally deficient vitamin B6 status, Caramel Colour III containing 23 (commercial sample) or 143 (research sample) ppm THI and administered at the level of the current acceptable daily intake of 200 mg/kg body weight/day for 7 days did not affect any of the factors investigated.

Administration, Oral↗
PubMed1991

Reversibility of thymic atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and bis(tri-n-butyltin)oxide (TBTO).

We studied the reversibility of thymic atrophy induced by intubation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 10 days after a single dose of 50 micrograms/kg, or bis(tri-n-butyltin)oxide (TBTO), 4 days after a single dose of 75 mg/kg. This was done by an experimental design in which the atrophic thymus was placed in an in vivo situation in which the toxic chemical was no longer present, e.g. by transplantation of atrophic thymic lobes in untreated normal rats with connection to the vasculature of the recipient. At 20 days after the transplantation, the atrophic thymus showed the morphology and architecture of a normal uninvoluted thymus: lymphocyte counts and phenotypic expression of markers on lymphocytes, epithelium, and macrophages in the transplanted lobe did not differ from those in untreated donor rats or those in the normal uninvoluted thymus. Considering the mechanism of action of the toxic chemical, TBTO has been claimed to affect preferentially (passenger) lymphocytes in the thymus: the recovery after transplantation therefore is explained on the mere influx of newly-recruited precursor cells from the bone marrow. For TCDD a toxic action on the stationary epithelial component of the thymus has been claimed. We conclude that this epithelial damage is reversible within the 3-week period of the present experiment, with respect to both the morphology and immunologic phenotype of epithelium and other cell populations, as well as the recruitment of lymphocytes.

Animals↗
PubMed1991

An enzyme-linked immunosorbent assay of anti-sheep red blood cell antibodies of the classes M, G, and A in the rat.

In order to investigate the immune system as a possible target for toxicity by chemicals, functional assays of the immune system are required. Sheep red blood cells (SRBC) are widely used as an antigen to study the immune competence of animals. Since routine toxicology includes data mainly provided with rat toxicity studies, there is a need for easy, specific, and reproducible assays of antibody responses to sheep erythrocytes in the rat. This report describes an enzyme-linked immunosorbent assay (ELISA) of anti-SRBC antibodies of the classes M, G and A in the serum of rats. Antigen preparations, prepared from ghosts of sheep erythrocytes by extraction with KCl, were used to coat the bottom of wells in 96 well microtiter plates. Serum samples from rats, that were immunized with sheep erythrocytes, were titrated on these plates, using specific polyclonal antibodies to rat immunoglobulins M and G, to which peroxidase was conjugated. Immunoglobulin A was assayed, using monoclonal anti-rat IgA antibodies, and polyclonal rat anti-mouse IgG that was conjugated with peroxidase. The results indicate that the ELISA of serum titers of IgM, G and A to sheep erythrocytes is an easy and reliable method, that can be used to detect the effects of chemicals on the immune system of the rat.

Animals↗
PubMed1991

Characterization of cloned chicken anemia virus DNA that contains all elements for the infectious replication cycle.

Circular double-stranded replication intermediates were identified in low-molecular-weight DNA of cells of the avian leukemia virus-induced lymphoblastoid cell line 1104-X-5 infected with chicken anemia virus (CAV). To characterize the genome of CAV, we cloned linearized CAV DNA into the vector pIC20H. Transfection of the circularized cloned insert into chicken cell lines caused a cytopathogenic effect, which was arrested when a chicken serum with neutralizing antibodies directed against CAV was added. Chickens inoculated at 1 day of age with CAV collected from cell lines transfected with cloned CAV DNA developed clinical signs of CAV. The 2,319-bp cloned CAV DNA contained all the genetic information needed for the complete replication cycle of CAV. The CAV DNA sequence has three partially overlapping major reading frames coding for putative peptides of 51.6, 24.0, and 13.6 kDa. The CAV genome probably contains only one promoter region and only one poly(A) addition signal. Southern blot analysis using oligomers derived from the CAV DNA sequence showed that infected cells contained double- and single-stranded CAV DNAs, whereas purified virus contained only the minus strand. It is the first time that the genome of one of the three known single-stranded circular DNA viruses has been completely analyzed.

Amino Acid Sequence↗
PubMed1990

Effects of ozone, hexachlorobenzene, and bis(tri-n-butyltin)oxide on natural killer activity in the rat lung.

The respiratory tract is a major route of exposure to noxious agents as well as pathogens such as viruses. Natural killer (NK) activity is an important first line of defense to virally infected cells as well as certain neoplasms; therefore, testing the effects of exposure to toxic compounds on this activity is important in understanding the immunotoxic potential of the compound. Lymphoid cell suspensions, obtained after enzymatic dispersion of rat lungs and purification over nylon wool columns, showed in vitro natural killer activity toward YAC lymphoma cells. Validation of the test with well-known NK activity stimulators such as Bacillus Calmette-Guérin (BCG), interleukin-2 (IL-2), interferon (IFN), and inhibitors like anti-asialo-GM1 (ganglio-n-tetrasylceramide) antibody confirmed the reliability of the test as an assay for detecting NK activity in rat lungs. Using this assay, we studied the effects of exposure to ozone (O3), hexachlorobenzene (HCB), and bis(tri-n-butyltin)oxide (TBTO) on NK activity in rat lung. Inhalation exposure to O3 for 7 days at 0.4 and 0.8 mg/m3 resulted in stimulation, and exposure at 1.6 mg O3/m3 resulted in suppression of NK activity. Oral exposure to HCB in concentrations of 150 and 450 mg/kg food for 6 weeks suppressed NK activity in rat lungs in a dose-related manner. This was also true for 6 weeks of oral exposure of rats to 20 and 80 mg TBTO/kg food, but to a lesser extent. In summary, we have developed and validated a method to measure the effects of (toxic) substances on NK activity in rat lung.

Animals↗
PubMed1990

Immunotoxicity of bis(tri-n-butyltin)oxide in the rat: effects on thymus-dependent immunity and on nonspecific resistance following long-term exposure in young versus aged rats.

To investigate whether immune function suppression observed in an earlier study after short-term bis(tri-n-butyltin)oxide (TBTO) exposure also occurred after long-term treatment, function studies for specific and nonspecific resistance were performed after exposure of weaned male rats to diets containing 0, 0.5, 5, or 50 mg TBTO/kg for 4-6 and 15-17 months. Treatment for 4.5 months had no effect on body weight but reduced thymus weight at 50 mg/kg. Regarding the thymus-dependent immunity, delayed-type hypersensitivity reactions to ovalbumin and tuberculin were not depressed, in contrast to the results of the short-term study. The resistance to the nematode Trichinella spiralis was dose-relatedly suppressed at the 5 and 50 mg/kg levels, in both experiments (5.5 and 16.5 months exposure), as shown by increased counts of muscle larvae and depressed serum IgE titers. Also the inflammatory reaction around cysts in parasitized musculature was reduced. No significant reduction was found in IgM and IgG titers to T. spiralis, ovalbumin, and sheep red blood cells as determined by enzyme-linked immunosorbent assay. TBTO exposure at 50 mg/kg for 4.5 months significantly reduced thymus weight, but the response of thymocytes to T-cell mitogens was unaltered. TBTO treatment for 4.5 or 16 months did not influence the response of spleen cells to T-and B-cell mitogens and neither influenced spleen weight. A dose-related shift was observed in T- and B- cell numbers in mesenteric lymph nodes as shown by flow cytometry using monoclonal antibodies: treatment for 6 and 18 months reduced the relative count of T-lymphocytes and consequently increased the percentage of B-lymphocytes. As a result, the T:B ratio was reduced in the 5 and 50 mg/kg groups. Concerning the nonspecific resistance, TBTO exposure for 5 and 17 months reduced macrophage function at 50 mg/kg as shown by impaired splenic clearance of Listeria monocytogenes bacteria. Natural cell-mediated cytotoxicity of spleen and peritoneal cells was investigated in a 51Cr-release assay with YAC-lymphoma target cells. TBTO treatment significantly suppressed natural killer (NK) activity in spleen cells. Significant suppression was noted in all treatment groups following 16 months TBTO exposure; in contrast to treatment for 4.5 months. No significant alterations were observed in the spontaneous cytotoxicity of nonadherent and adherent peritoneal cells following 4.5 months treatment. Treatment of aged (i.e., 1-year-old) male rats for 5 months with the 50 mg/kg diet reduced thymus weight but had no effect on body or spleen weight.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1989

Subacute toxicity of Zwittergent administered intramuscularly.

In order to assess the systemic toxicity of Zwittergent 3-14, a detergent used in the protein-detergent complex vaccines for its attractive immunogenic properties, a subacute toxicity study was performed. In this 4-week toxicity experiment five female and five male rats per group were injected intramuscularly with 0.25 ml of 0, 75, 750 and 7500 micrograms Zwittergent ml-1 sterile saline solution. Body weight and food intake were recorded weekly. At day 24 urine was collected for semiquantitative (pH, protein, ketone bodies, bilirubin and occult blood) and quantitative analyses (protein, creatinine and volume). At the end of the experiment blood was sampled for haematological [haemoglobin (Hb), packed cell volume (PCV), erythrocytes, leucocytes, reticulocytes and thrombocytes and differential white blood cell count] and biochemical analyses (alanine aminotransferase and aspartate aminotransferase. At necropsy brain, heart, liver, kidneys, spleen, thymus, adrenal glands, thyroid, pituitary gland, uterus, ovaries and testes were weighed. The underlined organs and the musculus quadriceps including the injection sites were examined histopathologically. Indications for systemic toxicity were noticed in the high-dose group and included occult blood in urine, elevated protein/creatinine ratio concomitantly with an increased urine volume and increased relative kidney weight indicating a slight disturbance of the kidney function. Some changes in haematological parameters (decreased PCV and increased numbers of thrombocytes eosinophils and monocytes) and a decreased glycogen content in the liver were recorded in the high dose group. These changes may be secondary to the extensive inflammatory reaction observed in the muscle of this high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1989

Application of diethylstilbestrol dipropionate in bulls. I. Excretion of residues in urine and faeces and histological and immunohistochemical changes in the prostate.

In this experiment 20 one year old bulls received a single intramuscular injection of the anabolic preparation diethylstilbestrol dipropionate (DES-DP) (an oil preparation or an emulsion). Four animals received a corresponding placebo. The application of DES-DP to bulls caused characteristic histological alterations in the peripheral glandular epithelium of the prostate, which could be observed until four weeks after treatment. The value of histological investigation as a screening method was, however, limited by the occurrence of only few metaplastic lesions and a rapid recovery. By contrast, immunohistochemistry using a polyclonal cytokeratin antiserum K40 appeared to be a specific and very sensitive method to detect oestrogen-induced lesions in the prostate. In only two animals, six weeks after injection with the DES-emulsion, false-negative results were obtained, demonstrating the potential value of this screening method. The excretion of DES in the urine and faeces was monitored using radioimmunoassay following chromatographic purification of the urine and faeces extracts. The excretion of DES in urine was faster for animals of the oil group. The DES content in urine decreased to the 1 microgram/l level after 42 days (emulsion group) or 70 days (oil group). The excretion in faeces was comparable to that in urine. After day 21 the excretion patterns of the two excreta were indistinguishable.

Animals↗
PubMed1988

Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection.

We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O3 concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also have a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats. This increased severity of the lesions after ozone exposure and subsequent infection with Listeria was presumably not a result of additive ozone and Listeria-induced lesions, but rather an effect of ozone-induced impaired clearance of the bacteria, caused by depressed macrophage activity and cellular immunity. T-cell-dependent immune responses form an important component of defense to respiratory infections with bacteria and viruses, and possibly also to neoplasms. Since our study unequivocally shows an effect on T-cell-dependent immunity, ozone exposure has to be judged potentially hazardous with respect to such challenges of the lung.

Animals↗