Extended histopathology in immunotoxicity testing: Interlaboratory validation studies

There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort was initiated. This study addresses the...

Repeated dose oral toxicological evaluation of concentrated barley β-glucan in CD-1 mice including a recovery phase

The cholesterol-lowering effect observed following consumption of oats and barley is attributable to the β-glucan component of the soluble fiber fraction of these cereal grains. β-Glucan has also been reported to modulate immune activity, however, few studies have evaluated the hematological effects of β-glucan following oral exposure. In the...

A study of the toxicity of five mineral hydrocarbon waxes and oils in the F344 rat, with histological examination and tissue-specific chemical characterisation of accumulated hydrocarbon material

Five food-grade mineral hydrocarbon (MHC) materials; a low melting point wax (LMPW), a synthetic wax (C80W) and three white oils (N15H, N70H and P70H) were administered orally to female Fischer-344 rats for 28 and 90 days at a dose level of 2% in the diet. Tissues were examined at autopsy for any treatment-related histopathological changes. The...

Rat monocyte-derived dendritic cells function and migrate in the same way as isolated tissue dendritic cells

Dendritic cells (DC) are the most potent antigen-presenting cells and are therefore useful to induce immune responses against tumor cells in patients. DC can be generated in vitro from monocytes using GM-CSF and IL-4, the so-called monocyte-derived DC (MoDC). To achieve antitumor responses, MoDC must be able to migrate to the draining lymph...

Comparison of dose-responses of contact allergens using the guinea pig maximization test and the local lymph node assay

The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are...

Coadministration of antigen and particles optimally stimulates the immune response in an intranasal administration model in mice

Some particulate matter is known to affect human health, yet the mechanism(s) by which it acts is largely unknown. One of the factors that may play a role in the immune- stimulating activity of particles is binding of allergen to particles. This may turn the particles into allergen carriers, resulting in antigen deposition within the altered...

Histopathologic approaches to detect changes indicative of immunotoxicity

Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is...

Monoclonal antibodies against the human mannose receptor as a specific marker in flow cytometry and immunohistochemistry for macrophages

Recently we developed mouse monocloual antibodies (mAb) against the isolated human 175-kDa mannose receptor. In the present study we tested whether these mAb are suitable for the detection of the mannose receptor on cultured macrophages using flow cytometry and on cells in human tissues using immunohistochemistry. Human monocytes did not react...

Increased adjuvant efficacy in stinulation of antibody responses after macrophage elimination in vivo

To investigate whether macrophages influence the efficacy of adjuvants, we locally eliminated lymph node macrophages with dichloromethylene diphosphonate containing liposomes before primary immunization. After macrophage elimination, animals were immunized with a soluble antigen (TNP-KLH; 2,4,6-trinitrophenyl-keyhole limpet haemocyanin) either...

Local lymph node activation in rats after dermal application of the sensitizers 2,4-dinitrochlorobenzene and trimellitic anhydride

Five rat strains were compared for their performance in the local lymph node assay (LLNA) a promising test system for the identification of the skin-sensitizing potential of chemicals in the mouse. The contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and the contact and respiratory sensitizer trimellitic anhydride (TMA) were used as model...

Histopathology of a spontaneously developing mast cell sarcoma in a Wistar rat

A case report is given of a very rare spontaneous mast cell tumor in the eyelid of the left eye of a female Wistar rat used in a long-term oral toxicity study. Metastasis of the tumor had occurred in the mandibular lymph nodes and in the liver. Clinically, the animal showed blepharospasm, dacryorrhoea, and exophthalmus. Hematologic findings...

Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and migration. After xenogeneic skin transplantation, we...

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: Involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes

Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until now no method for the subcellular detection of...

Cytotoxic potential of CD8+ T-cells in lymphoid follicles during HIV-1 infection

Enhancement by drugs of metastatic lung nodule formation after intravenous tumour cell injection

In studies on a model of induced pulmonary metastasis in mice a tumour host system was analysed which was not affected by immunogenicity of the tumour for the host; neither intensive immunosuppression nor immunization caused a significant change in the quantity of pulmonary metastatic nodules. In contrast the application of cytostatic drugs and...

Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administration. Data were also obtained regarding the...