Biomedical subjects

J H Dean

Publications and source records attributed to J H Dean.

At least 55 records · Page 3Linked to original sources

PubMed1986

Persistent suppression of humoral and cell-mediated immunity in mice following exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene.

Carcinogen-induced immunosuppression has been implicated as an epigenetic mechanism in promoting the outgrowth and metastasis of neoplastic cells. It has previously been reported that the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) suppresses both humoral immunity (HI) and cell-mediated immunity (CMI) 3-5 days following exposure. Since persistent systemic immunosuppression may be more relevant in tumor outgrowth, assays quantitating HI and CMI, including those functions involved in tumor resistance, were performed 4 and 8 weeks following exposure to tumorigenic doses of DMBA. Adult B6C3F1 female mice were administered DMBA dissolved in corn oil subcutaneously at 5, 50 and 100 micrograms/g body weight in ten equal doses over 2 weeks (corn oil = vehicle control). The number of splenocytes producing IgM antibody to the T-dependent antigen, sheep erythrocytes, was suppressed up to 95% and 98% at 4 and 8 weeks, respectively. The IgG response was similarly depressed 75% and 98% at 4 and 8 weeks, respectively. Lymphoproliferation of splenocytes in response to the mitogens LPS, PHA and Con A were depressed up to 88%, 78% and 83% at 4 weeks and 63%, 63% and 67% respectively, at 8 weeks. In addition, alloantigen-induced proliferation of splenocytes in a one-way mixed lymphocyte culture was suppressed up to 90% at 8 weeks. The ability to generate cytotoxic T-lymphocytes (CTL) in vitro against P815 tumor cells was depressed at both time periods (88% and 60%, respectively) as was natural killer (NK) cell cytolysis of YAC-1 tumor targets (84% and 55%, respectively). The immunosuppression noted in these parameters was similar to that observed within 3-5 days following DMBA dosing. The persistent immunosuppression induced by the PAH carcinogen DMBA, including CTL and NK cell tumoricidal functions, may represent an important epigenetic mechanism contributing to tumor outgrowth or metastasis by this class of agents.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

Immunological studies in B6C3F1 mice following exposure to ethylene glycol monomethyl ether and its principal metabolite methoxyacetic acid.

Exposure to glycol ethers has been associated with adverse effects in laboratory animals including thymus atrophy and mild leukopenia. These effects may involve depletion of immunoresponsive cells. This study examined possible alterations in immune function and host resistance of B6C3F1 mice following exposure to ethylene glycol monomethyl ether (EGME) or its principal metabolite, methoxyacetic acid (MOAA). EGME and MOAA were administered by gavage to mice in 10 doses over a 2-week period at total dosages of 250, 500, and 1000 micrograms/g of body weight. Following exposure, immunopathology, humoral immunity, cell-mediated immunity, macrophage function, and host resistance to Listeria monocytogenes bacterial challenge were examined. A 48% reduction in thymus weight was observed at the intermediate and high doses of both chemicals. No significant alterations in immune function or host resistance to L. monocytogenes were observed in animals exposed to either EGME or MOAA.

Acetates↗

PubMed1985

Correlation of murine susceptibility to tumor, parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the tumor promoter phorbol myristate acetate.

Phorbol myristate acetate (PMA), the most potent of the tumor promoting phorbol diesters, modulates function in several immunoresponsive cells following in vitro exposure. Since suppression of cellular mechanisms capable of limiting tumors and infections can adversely affect health, these experiments were designed to evaluate relevant components of cell-mediated immunity (CMI) following in vivo PMA exposure, and to determine the biological significance of any alterations utilizing assays of host resistance. Adult, female B6C3F1 mice were administered 0.2, 2.0, 20.0 or 40.0 micrograms PMA/g body weight subcutaneously over a two-week period. Mechanisms of cell-mediated host resistance were assessed by quantitating natural killer (NK), cytotoxic T-lymphocyte (CTL) and macrophage-mediated lysis of radiolabelled tumor target cells, and macrophage-induced cytostasis in tumor cell populations. Macrophages from PMA-treated mice were cytostatic to tumor cells, inhibiting up to 90% of growth in cultured tumor cells, but were not tumoricidal. Furthermore, pyran-elicited (primed) macrophages, which are activated to fully cytotoxic states by in vitro exposure to lipopolysaccharide, were inhibited in tumoricidal activation by in vivo PMA exposure. The induction of responsive but not cytotoxic macrophages by in vivo PMA exposure is consistent with the enhanced resistance to Listeria bacterial challenge, and increased susceptibility to B16F10 tumor and Trichinella parasitic challenges observed in these mice. Furthermore, previous reports of decreased in vitro NK activity following in vivo PMA exposure and present observations of correlative decreases of in vivo NK activity (55% decrease in mice exposed to 20 micrograms PMA/g) suggest an important role for NK activity in limiting in vivo B16F10 melanoma growth. CTL effector function was less susceptible to PMA-induced suppression than NK function at similar dosages, further supporting a predominant role of macrophages and NK cells or possibly other effector functions in the resistance to Listeria, Trichinella, or B16F10 challenge. Nevertheless, significant suppressive effects of PMA on CTL function at higher dosages cannot be excluded as contributing to altered host resistance to these agents. These studies demonstrate that in vivo exposure to PMA can modify cell-mediated mechanisms of host resistance with coincident alterations in the incidence of infections and tumors.

Animals↗

PubMed1985

Mechanisms of dimethylbenzanthracene-induced immunotoxicity.

Traditional methods for toxicological assessment have implicated the immune system as a frequent target organ of toxic insult following chronic exposure to certain environmental chemicals, radiation or therapeutic drugs (xenobiotics). Immunotoxicity is expressed as autoimmunity, chemical hypersensitivity or immunosuppression. A tiered approach for characterizing chemical and drug-induced immunomodulation has been developed and validated in laboratory animals. Polycyclic aromatic hydrocarbons (PAH) have been studied because of their ubiquitous presence in the environment and carcinogenic potential. Since immunosuppression induced by PAH carcinogens has been implicated as an epigenetic mechanism in the outgrowth of initiated cells, this tiered approach was used to characterize the mechanism of PAH immunosuppressive capacity. Previously, studies in this laboratory have demonstrated that subchronic exposure of B6C3F1 mice to PAH carcinogens suppresses both humoral immunity (HI) and cell-mediated immunity (CMI), concurrently with decreased resistance to tumor challenge. The potent carcinogenic PAH, 7,12-dimethylbenz[a]anthracene (DMBA) was subchronically administered subcutaneously at 5, 50, or 100 micrograms/g of body weight. Natural killer (NK) cell tumor cytolysis, generation of cytotoxic T-cells (CTL), and lymphoproliferation to mitogens and allogeneic splenocytes in mixed leukocyte cultures (MLC) were quantitated 3-5 days after exposure to assess CMI. Mitogen and alloantigen-induced proliferation (MLC) of splenocytes was suppressed up to 90%. CTL and NK tumor cytolysis of radiolabelled target cells were similarly depressed up to 88 and 82%, respectively. Impairment of MLC or CTL responses correlated with increased susceptibility to challenge with PYB6 sarcoma cells. HI was measured by quantitating the number of antibody (IgM) plaque-forming cells (PFC) produced in response to T-cell dependent antigen challenge (sheep erythrocytes) and was similarly suppressed up to 95%. To understand the mechanism of PAH-induced immunotoxicity, splenocytes from DMBA-exposed mice were sensitized to alloantigens in the presence of interleukin-2 (IL-2) because there were indications that T-helper cell function was suppressed. In these preliminary studies, CTL suppression could be completely restored by the addition of the T-cell growth supporting lymphokine (IL-2) during the inductive phase of CTL generation, suggesting that DMBA exposure directly or indirectly induced deficits in T-helper cell function.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1984

The concurrence of Saethre-Chotzen syndrome and malignancy in a family with in vitro immune dysfunction.

The occurrence among 13 siblings of a malformation-mental retardation syndrome and diverse malignancies was investigated for etiologic relationship by clinical, genetic, immunologic, and virologic techniques. Three sisters and their father had Saethre-Chotzen syndrome, an autosomal dominant trait with craniosynostosis and asymmetric facies. One affected sister also had nasopharyngeal carcinoma; tow nondysmorphic brothers had Hodgkin's disease, and another had seminoma with teratocarcinoma of the testis. Decreased in vitro lymphocytic proliferation to various mitogens was observed in both available siblings with tumor, one sibling with Saethre-Chotzen syndrome, and two clinically normal siblings and their father. Both parents and all siblings had normal karyotypes and no increase of antibodies to Epstein-Barr virus. The malformation syndrome and the various neoplasias segregated independently of each other and of 47 genetic markers, including histocompatibility antigens (HLA). This study illustrates an approach to defining etiology when rare disorders cluster in a family and suggests that the occurrence of malignancies in this family may be related to subclinical immune dysfunction. Whether the Saethre-Chotzen syndrome predisposed to malignancy, perhaps through impaired immunity, awaits additional observations.

Acrocephalosyndactylia↗

PubMed1984

Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice. I. Effects on humoral immunity and host resistance.

It has previously been demonstrated that the polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (B[a]P), suppresses the terminal step in B-cell differentiation, resulting in a decrease in antibody production to T-dependent and B-2 T-independent antigens. The purpose of this study was to ascertain if this effect was common to carcinogenic PAHs or specific for B[a]P. The PAH 7,12-dimethylbenz[a]anthracene (DMBA) was administered to B6C3F1 female mice by ten sc injections of 0.5, 5, or 10 micrograms/g over a 2-week period (i.e., total dose of 5, 50, and 100 micrograms/g). Immune function and host resistance assays were performed 3 to 5 days following the last injection. The 10 micrograms/g dosage resulted in a marked decrease in spleen weights and spleen and bone marrow cellularity, while thymus and body weights were not significantly altered. The ability to generate B-lymphocyte colonies in vitro from spleen precursor cells was also suppressed at the 10 micrograms/g dose. Exposure to DMBA at 5 micrograms/g or greater resulted in a reduction of up to 97% in the number of IgM plaque-forming cells in response to the T-dependent antigen sheep red blood cells (SRBC). The IgG response to SRBC was similarly depressed. The IgM response to the hapten-conjugated T-independent antigens trinitrophenyl-lipopolysaccharide (TNP-LPS) (specific for B-1 cells) and trinitrophenyl (TNP)-Ficoll (specific for B-2 cells) was also depressed (88 and 97%, respectively) at 10 micrograms/g. DMBA exposure resulted in an increased susceptibility to challenge with the PYB6 transplantable sarcoma and the bacterium Listeria monocytogenes, in contrast to B[a]P exposure, which had no effect on host resistance assays. Thus, DMBA, a more potent carcinogen than B[a]P, produces a more extensive B-cell suppression than B[a]P as well as alters host resistance to tumor and bacterial challenge.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1984

Studies of immune function and host resistance in B6C3F1 mice exposed to formaldehyde.

A series of immune function and host resistance parameters were examined in female B6C3F1 mice following a 21-day (6 hr/day) inhalation exposure to 15 ppm of formaldehyde (HCHO). Immune parameters examined included delayed hypersensitivity to keyhole limpet hemocyanin, antibody plaque-forming cell response to sheep erythrocytes (T-lymphocyte-dependent antigen) and TNP-Ficoll (T-lymphocyte-independent antigen), lymphoid organ weights and histopathology, routine hematology, bone marrow cellularity and CFU progenitor cell enumeration, lymphocyte subpopulation quantitation by cell surface markers, mitogen-induced lymphocyte blastogenesis, macrophage function parameters, and host resistance to challenge with the bacterium Listeria monocytogenes and transplantable tumor cells. Lymphoid organ weight, bone marrow cellularity, and hematology parameters were unchanged in HCHO exposed mice. Similarly, the percentage of T and B lymphocytes and their proliferative responses to mitogens were not significantly altered. Antibody (IgM) plaque-forming cell response following antigen challenge was unchanged. Macrophage function was normal although some evidence of enhanced H2O2 production associated with elevated bactericidal activity was observed in resident macrophages. Resistance to challenge with the bacteria Listeria monocytogenes was significantly enhanced, while resistance to tumor challenge remained unchanged. No evidence of immunosuppression following short-term exposure to HCHO was observed.

Animals↗

PubMed1984

Bone marrow alterations induced in mice with inhalation of chrysotile asbestos.

The effect of chrysotile asbestos exposure on bone marrow and immune parameters was examined in mice at 2, 12, and 26 weeks following a 3-day inhalation exposure. Ultrastructural examination revealed that the fibers were deposited primarily at alveolar duct bifurcations within the centriacinar region of the lung. Histological pulmonary changes were minimal, but by 26 weeks early asbestosis characterized by clusters of macrophages and minimal fibrosis were present in the centriacinar region of the lung. Lymphoproliferative responses, antibody levels, and number of plaque forming cells were not significantly altered in exposed mice. Pulmonary macrophages, but not peritoneal macrophages, showed evidence of activation in the chrysotile-exposed mice at 26 weeks following exposure. The most striking change was the depression of the number of bone marrow pluripotent stem cells (CFU-S) and marrow granulocyte macrophage progenitors (CFU-GM) which were lower at all three postexposure examinations. It is felt that the depression of bone marrow progenitors in asbestos-exposed mice may have relevance to the leukopenia reported in workers with occupational history of asbestos exposure.

Animals↗

PubMed1984

Altered host resistance to Trichinella spiralis infection following subchronic exposure to diethylstilbestrol.

The effects of subchronic exposure to diethylstilbestrol on the host response to infection with Trichinella spiralis were examined in adult B6C3F1 mice. Expulsion of adult Trichinella from the small bowel, intestinal inflammation and delayed hypersensitivity responses to Trichinella antigens in artificially sensitized mice were investigated. Administration of 8 micrograms/g of diethylstilbestrol for five consecutive days beginning on days -5,0, +3 or +8 of infection inhibited adult worm expulsion and tissue reactions in the small intestine. Expulsion of adult parasites was also delayed in mice given 0.2 microgram/g of diethylstilbestrol for the first five days of infection. When the chemical was given during a primary infection, mice failed to expel a second infection as rapidly as untreated controls or previously infected mice exposed during a second infection. These findings indicate that diethylstilbestrol exposure altered the immune responses that mediate expulsion of adult worms from the gut, especially when exposure occurred during the inductive phase of host immunity. These results also suggest that use of diethyl-stilbestrol as a weight-gain promoter may lead to increased parasite burdens. While diethylstilbestrol-exposed mice retained adult worms longer than controls, no significant increase was found in numbers of encysted muscle-phase larvae, contrary to the usual findings in animals maintaining adult worm burdens for extended periods. The possibility that macrophages activated by diethylstilbestrol treatment had a role in limiting larvae encystment in the host musculature is discussed.

Animals↗

PubMed1984

Estrogen immunosuppression is regulated through estrogenic responses in the thymus.

Previous studies have clearly established that physiologic and pharmacologic levels of estrogens modulate immunologic responses that result in simultaneous activation of the reticuloendothelial system and depression of cell-mediated immunity. The mechanisms of estrogen immunoregulation were examined in adult female mice administered pharmacologic levels of exogenous estrogens. Evaluation of steroidal and nonsteroidal compounds with varying degrees of estrogenicity (i.e., uterotrophic activity) provided evidence that their immunotoxicity, for the most part, correlates with estrogenicity. The mechanisms responsible for these effects appear to be complex, mediated through a direct chemical interaction with lymphoid target cells, as well as with nonlymphoid tissue, resulting in the release of soluble immunoregulatory factors. The latter phenomenon was examined in detail and it appears to constitute a regulatory factor(s) produced by thymic epithelium in response to an estrogen stimulus. This response is not only estrogen specific but may involve specific binding to estrogen receptors or receptor-like structures present in cytosol preparations from thymic epithelial cells.

Animals↗

PubMed1983

Immunological and biochemical responses in mice treated with mercuric chloride.

Adult B6C3F1 male mice were given water containing 3, 15, and 75 ppm mercury (as mercuric chloride) for 7 weeks. There were dose-related increases in blood and kidney mercury levels but only the former showed a time-dependent change. Mercury was not detected in any of the lymphoid organs except for the spleen. There was no mortality and only minimal histological changes occurred in kidneys of dosed mice. Nonspecific toxicity occurred at the 75 ppm dose level, consisting of small differences in body and organ weights, hematological changes, and general enzyme inhibition in the bone marrow and spleen. However, there were specific immunotoxic and biochemical alterations in lymphoid organs of mice treated at the lower doses of mercury. The immunological defects were consistent with altered T-cell function as evidenced by decreases in both T-cell mitogen and mixed leukocyte responses. There was a particular association between the T-cell defects and inhibition of thymic pyruvate kinase, the rate-limiting enzyme for glycolysis. The differences in the pattern of enzyme responses among lymphoid organs implied that two mechanisms of mercury toxicity were operative--one at high concentrations that caused physicochemical enzyme inhibition and another at low concentrations that caused indirect enzyme inhibition.

Animals↗

PubMed1983

Selective immunosuppression resulting from exposure to the carcinogenic congener of benzopyrene in B6C3F1 mice.

B6C3F1 mice were exposed to two congeners of benzopyrene, either the carcinogen benzo(a)pyrene (B(a)P) or the non-carcinogen benzo(e)pyrene (B(e)P. Exposure of mice to B(a)P resulted in a reduced number of IgM and IgG antibody plaque forming cells (PFC) to the T-dependent (TD) antigen SRBC and IgM PFC's to the T-independent (TI) antigen LPS. The IgM response to hapten conjugated TI antigens was examined using TNP-LPS for reactivity of less mature B cells (B1) and TNP-Ficoll for more mature B cells (B2). Exposure to B(a)P severely depressed the TNP-Ficoll PFC response by up to 77% without altering the TNP-LPS response. These data indicated that exposure to B(a)P alters differentiation and antibody production in mature B cells to both TD and B2 TI antigens. No change in PFC was observed following exposure to B(e)P. Mishell-Dutton co-cultures confirmed that B cells were affected and that T helper cells or suppressor Mphi were not involved. Parameters of cell-mediated immunocompetence including delayed cutaneous hypersensitivity to KLH, allograft or tumour cell rejection and susceptibility to Listeria monocytogens were unaltered in B(a)P treated mice.

Animals↗

PubMed1983

Effect of pyran copolymer on activation of murine macrophages: evidence for incomplete activation by use of functional markers.

The degree of activation of peritoneal macrophages elicited by pyran copolymer (MVE-2) was studied in C57BL/6J mice. When cytotoxicity was examined under endotoxin-free culture conditions, the pyran-elicited macrophages could not complete cytolysis of tumor target cells. The macrophages, however, completed cytolysis when pulsed with endotoxin. These results were obtained when either the interval between injection of the pyran copolymer and harvest of the macrophage or the dose of pyran was varied. The pyran-elicited macrophages expressed five markers considered to be typical of inflammatory macrophages, and bound tumor cells to an augmented degree. The pyran-elicited macrophages were capable of secreting a potent cytolytic proteinase when pulsed with endotoxin, but did not secrete cytolytic proteinase spontaneously. The pyran-elicited macrophages, in contrast to inflammatory macrophages, could effect cytostasis of tumor cells; their cytostatic potential was also augmented by addition of endotoxin. Taken together, the results indicated that pyran copolymer elicits primed but not fully activated murine macrophages.

Animals↗

PubMed1982

Assessment of myelotoxicity caused by environmental chemicals.

Potential antineoplastic agents must be screened for the delayed toxicity that occurs in many cases of drug-induced bone marrow aplasia. In vitro clonal assays for hematopoietic progenitor cells have been developed to assess the degree of myelotoxicity. This adverse side effect is often the limiting factor in the development of new cancer chemotherapeutics. In addition, many environmental chemicals are cytotoxic to rapidly proliferating cells, but a systematic assessment of their myelotoxicity has not been performed. We have used clonal marrow assays to investigate a panel of chemicals including 2,3,7,8-tetrachlorodibenzo-p-dioxin, polybrominated biphenyls, diethylstilbestrol, benzo(a)pyrene and indomethacin. All were immunotoxic, some to pleuripotent hemopoetic stem cells and other to granulocyte-macrophage progenitors, and at concentrations below those causing other toxic manifestations. This shows that these bone marrow clonal assays, and hopefully future one for erythroid, B- and T-lymphocytes, and megakaryocytes, will provide the specificity and sensitivity necessary to delineate the myelotoxicity of a broad spectrum of environmental chemicals.

Animals↗

PubMed1982

Methods and approaches for assessing immunotoxicity: an overview.

The goals of the National Toxicology Program as they relate to immunological evaluation in toxicity assessment are discussed. The advantages of immune function assays for defining cellular injury as subtoxic levels following exposure to general or immunocyte specific chemical toxicants are proposed. A comprehensive screening panel of immune function and host resistance assays is presented in the context of an NIEHS approach for immunotoxicity assessment and methods selection. A second panel for defining the mechanism underlying immunological injury was also described. Studies utilizing these methods and approaches are described in companion papers by our group.

Drug Evaluation, Preclinical↗

PubMed1982

Cell-mediated immunity and its application in toxicology.

A variety of in vivo and more recently in vitro assays have been described to assess cell mediated immunity (CMI). Two methods routinely employed in our laboratory to assess CMI following exposure to chemicals in rodents include delayed hypersensitivity and in vitro lymphoproliferation. Preliminary studies indicate that depressed delayed hypersensitivity responses, as performed by a radiometric assay, correlates with altered susceptibility to infectious agents and tumor cell challenge following exposure to immunotoxic chemicals. Furthermore, suppression of T-cell lymphoproliferative responses to at least 50% below control values correlated with depressed delayed hypersensitivity responses and altered host susceptibility. On the other hand, when suppression of T-cell lymphoproliferative responses are within 50% of control values, delayed hypersensitivity and host susceptibility parameters are not affected. Assuming adequate technical expertise and accurate data interpretation, CMI assays of these types can provide a valuable data base for toxicology studies and immunotoxicity assessment.

Animals↗

PubMed1982

Application of tumor, bacterial and parasite susceptibility assays to study immune alterations induced by environmental chemicals.

Model systems to study the effects of chemicals of environmental concern on bacterial and parasitic diseases as well as the immunosurveillance and destruction of transplantable tumor cells were described and evaluated. Studies were conducted in female B6C3F1 mice following adult or pre/postnatal exposure to several prototype chemicals. The prototype chemicals employed included the synthetic estrogen diethylstilbestrol (DES), the polycyclic aromatic hydrocarbon benzo(a)pyrene (B[a]P), and the carcinogenesis promoting agent 12-0-tetradecanoyl-phorbol-13-0-acetate (TPA). The host resistance models employed depend primarily on functional thymus-dependent immunity, although humoral immunity is suggested to have a role in the parasite model as well. These models include: subcutaneous challenge with a dose of PYB6 tumor cell causing a 10-20% incidence (TD(10-20)) of tumor; intravenous challenge with B16 melanoma cells; challenge with a dose of Listeria monocytogenes causing a 10-20% incidence of mortality (LD(10-20)); challenge with a dose of E. coli lipopolysaccharide endotoxin causing a 10-20% incidence of lethality (LD(10-20)); and challenge with larvae of Trichinella spiralis for parasite expulsion kinetic studies. Increased mortality was observed following Listeria monocytogenes challenge in DES-exposed mice. B(a)P and TPA exposure did not alter host resistance to this organism. The increased mortality observed following DES was associated with a significant increase in the number of viable Listeria in the spleens and livers at 4 days, a time when T-cell immunity is thought to be expressed, but bacterial counts were similar to control mice at day 1, a time when MPhi are thought to exert their greatest effect. These data suggest that the increased Listeria susceptibility found following DES exposure may result from a T-cell defect, although the intracellular killing capacity of DES-treated Mvarphi's has not been well examined. Tumor susceptibility studies following challenge with 5 x 10(3) viable syngeneic PYB6 tumor cells revealed that nontreated adult B6C3F1 mice resisted tumor formation, with only a 10-20% incidence of tumor formation. In contrast, mice exposed to DES or TPA as adults had a tumor frequency of from 70-100% following TPA and up to 90% following DES exposure. In all cases the tumors were progressive and resulted in death. B(a)P did not alter the frequency of tumor incidence from controls in this model. Preliminary data, using the B16 melanoma intravenous challenge model and (125)IUdR to quantitate tumor mass revealed this model was sensitive to non-specifically activated macrophage kill. DES treated mice with activated macrophages did not demonstrate increased tumor mass, while mice exposed to TPA or the potent immunosuppressive agent cyclophosphamide had a significantly increased tumor mass in their lungs. Expulsion of Trichinella spiralis adults from the gut also apparently required functional T-cells and possibly some element of humoral immunity. Mice exposed to DES and B(a)P exhibited increased numbers of adult worms in the gut at day 14. Sensitivity to gram-negative endotoxin (LPS) was apparently increased following exposure to DES or B(a)P. These data suggest that the detoxification of LPS is related to an intact Mvarphi population. The data presented here demonstrate the sensitivity of the host resistance assay panel proposed for detecting immune alteration. Alteration of T-cell function appeared to correlate with increased susceptibility to bacterial and tumor cell challenge.

Animals↗

PubMed1982

Peritoneal macrophage alterations caused by naturally occurring mouse hepatitis virus.

During routine harvest of murine resident peritoneal cells for macrophage function assays the authors recently noted that mice showed a 3-4-fold spontaneous increase in number of peritoneal cells within 1 week of being placed in one of their animal rooms. While the mice appeared clinically normal, the collected macrophages had highly convoluted membranes, showed enhanced spontaneous tumor cell killing, and showed increased erythrophagocytosis. Histopathologic findings included mild peritonitis and occasional foci of individual hepatocyte necrosis. The results of routine murine serologic studies and bacterial cultures of the peritoneal cavity were negative. Immunosuppressed mice placed in this room showed severe hepatic necrosis within 4 days, and ultrastructural particles characteristic of corona virus could be demonstrated in the necrotic foci. Mouse hepatitis virus (MHV) was isolated from these livers. Untreated mice showed positive MHV titers, as detected by the enzyme-linked immunoabsorbent assay (ELISA) after 21 days in the room. This episode demonstrates that MHV have profound effects on macrophage parameters while causing few clinical signs or histopathologic alterations. Secondly, the complement fixation assay for MHV as included in routine viral screens appears relatively insensitive for detecting outbreaks of MHV.

Animals↗