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Biomedical subjects

L D Koller

Publications and source records attributed to L D Koller.

At least 55 records · Page 3Linked to original sources

In vitro assessment of humoral immunity following exposure to heavy metals.

The immune system of animals and man is extremely complex. This report will discuss the effect metals has on one segment of the immune system; that is, humoral immunity. Humoral immunity is essentially the production of antibody in response to an antigen. The B-lymphocyte is the primary cell responsible for producing antibody. However, this cell is regulated by T-lymphocytes and macrophages. Many methods are available to assess humoral immune responses. A multitude of immunoassays have been developed for enumeration of serum antibody. Some of these are immunodiffusion, complement fixation, serum neutralization, hemagglutination, radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Detection of antibody-forming cells distinguishes between effect on antibody production compared to degradation of preformed antibody. Other available methods are measurement of surface receptor (Fc and complement) activity on B-cells. Mitogens (T-independent) have also been regarded as a measurement for humoral immunity. In our laboratory, we have developed an ELISA technique that is appropriate for general assessment of humoral immune responses resulting from chemical exposure. This technique is highly sensitive and can be mechanized. The assay can easily be incorporated into the drug and chemical efficacy testing programs of industry.

Antibody Formation↗

Effects of transplacental exposure to chlorinated phenols.

Female rats were exposed to 0, 5, 50 or 500 ppm of 2-chlorophenol (2-CP) or pentachlorophenol (PCP). The study was designed to produce progeny which were exposed to the chlorophenolic compounds both prenatally and postnatally. Percent conception, litter size, birth weight, and number of stillbirths was determined at parturition. Hematologic parameters and body weights of the progeny were recorded at weaning age (3 weeks). Effects on reproduction were observed in both the 2-CP and PCP-exposed groups, as indicated by decreased litter sizes and increased number of stillborn. The data indicate that these chlorinated phenolic compounds may be feto- or embryotoxic at high doses. Effects on hematologic parameters were not observed. Further study involving transplacental and chronic exposures to these chlorophenolic compounds appears warranted.

Animals↗

Response of lymphocytes from lead, cadmium, and methylmercury exposed mice in the mixed lymphocyte culture.

Mice were exposed to various dosages of lead, cadmium, or methylmercury for 10 weeks. At the end of the feeding trial, splenic lymphocytes were evaluated for responsiveness in mixed lymphocyte cultures. Cadmium and methylmercury as well as one dose level of lead tended (not significant) to stimulate the lymphocyte reaction. These results are discussed and compared to other investigations concerned with the effect these environmental contaminants have on the cell mediated immune response of animals.

Animals↗

Effects of lead, cadmium and methylmercury on immunological memory.

The memory response of lymphocytes to antigen was altered in mice exposed to lead, cadmium, or methylmercury. Both lead (1300 ppm) and methylmercury(10 ppm) impaired the memory response while cadmium (300 ppm) stimulated memory. Memory was significantly affected only at the largest dosages where toxic signs were generally detected. The lower dosages did not affect the memory of lymphocytes which produce antibody. These data suggest that the T lymphocyte rather than the B lymphocyte is the cell affected when the secondary immune response is altered after exposure to subclinical amounts of these environmental contaminants.

Animals↗

Immunotoxicology studies of sodium arsenate-effects of exposure on tumor growth and cell-mediated tumor immunity.

Exposure of mice to sodium arsenate (Na2HAs04) at levels of 2.5, 25 and 100 ppm As in the drinking water for 10-12 weeks increased the latent period and decreased the incidence of tumors induced by injection of MSB sarcoma cells. Tumor growth and regression induced by Moloney sarcoma virus (MSV) was not significantly affected by arsenic exposure. Cell mediated tumor immunity was either unaffected or enhanced by exposure to arsenic. Our results indicate that chronic exposure to sodium arsenate at arsenic levels as high as 100 ppm is not detrimental to mice in terms of tumor growth and immunosuppression.

Animals↗

Some immunological effects of lead, cadmium and methylmercury.

Environmental contaminants may alter one specific or several segments of the immune response. It is often necessary to examine each parameter (humoral, cell-mediated and macrophage) to assess the extent that each is involved. Lead and cadmium exposure results in suppression of many aspects of the immune response of animals. This suppression often occurs at very low subclinical dosages and therefore is detrimental to the health of animals and perhaps man by methods other than the typical well-documented toxicity which results at larger dosages. Methylmercury has been shown to inhibit the primary, secondary and memory immune response but few studies have described possible effects on T lymphocytes and macrophages. The effect that methylmercury imposes on the immune system needs further investigation.

Animals↗

Effect of cadmium exposure on primary tumor growth and cell-mediated cytotoxicity in mice bearing MSB sarcomas.

In vivo MSB tumor growth and cell-mediated cytotoxicity (CMC) to MSB tumor cells in vitro were studied in male C57BL/6 mice exposed to 0, 3, 30, or 300 ppm Cd as CdCl2 in their drinking water for 21 weeks prior to and during tumor growth. CMC was assessed on days 5, 12, and 19 post injection with the use of both a 51Cr release assay and a 51Cr post-label assay. Cd exposure significantly inhibited the growth of MSB tumors in vivo and enhanced the levels of CMC in the tumor-bearing hosts. Peak levels of CMC on day 12 post tumor injection were significantly increased in Cd-exposed animals. However, whereas the inhibition of tumor growth was directly dependent on the dose of Cd, the enhancement of CMC was inversely related to dosage. These data suggested that other mechanisms in addition to increased CMC were involved in tumor growth inhibition. Possible factors such as direct inhibition of tumor growth by Cd and decreased serum blocking levels in Cd-exposed animals are discussed.

Animals↗

Evaluation of data from mitogen studies in CBA mice: comparison of counts per minute, stimulation index and relative proliferation index.

Lymphocyte proliferation assays were conducted on splenic lymphocytes collected from CBA mice that had been exposed to lead acetate or cadmium chloride for 10 weeks. The ability of mitogens concanavalin A and lipopolysaccharide, as well as purified protein derivative, to induce proliferation in vitro in the presence or absence of macrophages was assessed. Data were compared by using counts per minute (cpm), stimulation index, and relative proliferative index. Data varied considerably within treatment groups performed on different days, which is a typical characteristic of mitogen proliferation investigations. According to cpm data, only 3 of 21 treatments were significantly (P less than 0.05) altered when compared with controls. The stimulation indices were highly influenced by background counts and frequently did not correlate with cpm. The relative proliferative index, on the other hand, calculates net cpm, closely corresponds to cpm, compensates for background counts and is affected less by variation than is the stimulation index, and selected cutoff values give a more sensitive measure for determination of altered proliferative responses when statistical procedures are not applicable. Effects of macrophages, carbon dioxide, and bovine fetal serum on lymphocyte transformation are discussed.

Animals↗

Methylmercury: effect on serum enzymes and humoral antibody.

Dosages of 20 and 10 ppm methylmercury were toxic to rabbits while 1 ppm did not produce clinical signs or death. Serum alkaline phosphatase levels were elevated in all rabbits exposed to methylmercury. Methylmercury-exposed rabbits challenged to A/PR8 influenza virus had hemagglutination inhibition titers as much as four times lower than those of controls. Histopathologic lesions were found in the cerebellum of rabbits that died. The most significant features of this study were that methylmercury chloride suppressed the humoral immune system and resulted in increased serum alkaline phosphatase levels, which may aid in diagnosis when methylmercury poisoning is suspected.

Alkaline Phosphatase↗