Mirtha Depiante-Depaoli

Experimental Autoimmune Damage to Rat Male Accessory Glands (MAG)

ABSTRACT: Isoimmunization of Wistar rats with male accessory gland (MAG) extract and complete Freunds adjuvant (CFA) induces a specific cell‐mediated immune response detected by skin delayed hypersensitivity, spleen lymphocyte culture as well as by the presence of macrophage inhibitory factor and skin reactive factor. Specific antibodies have also been investigated by hemagglutination, immunodiffusion, and complement‐fixation tests. In a group of rats receiving a single immunizing dose no antibody response was detected, but in 5 out of 8 rats a cell‐mediated immune response was found accompanied in three of them by mild histological changes in the target organ. In a second group that underwent a more intense and extended immunization schedule, the humoral response was detected by complement fixation in only three undiluted sera. The cellular immune mechanism was found in 18 out of 20 rats through one or more of the tests in the study. Male accessory gland lesions in various degrees were observed in 15 cases and they were mainly represented by mononuclear infiltration. Whether a cell‐mediated or humoral mechanism is responsible for induction of the tissue damage observed in the target glands is discussed.

Experimental Autoimmune Damage to Rat Male Accessory Glands. II. T Cell Requirement in Adoptive Transfer of Specific Tissue Damage

ABSTRACT: Experimental autoimmune vesiculoprostatitis (EAVP) was transferred within inbred Wistar rats by a relatively small number of spleen cells obtained 30 days after immunization of donors with MAG extract in CFA and injected in the internal jugular vein of recipients. Specific tissue alterations identical to those present in the glands of the donors were observed 7 days after the transfer of the cells. The main alteration present was infiltration of mononuclear cells in the interstitium accompanied by fibrosis in more severe cases and flattening of epithelium in the ventral and dorsal prostate, seminal vesicle, and occasionally in coagulating gland. Nine out of ten recipients developed sexual accessory glandular lesions of various degrees. No histological alterations were observed in the absence of cell‐mediated immune response and extensive damage was only observed in rats expressing two or more positive assays. The separation of the transferred cells into enriched population of T and B cells has proved that T lymphocytes are required for the production of the tissue lesions. Depletion of T lymphocytes by nylon wool separation and anti‐rat thymocytes serum and complement completely abrogate their capacity to transfer the glandular alterations. Furthermore, specific antibody precursor cells on their own seem to be incapable to promote the antibody synthesis and to initiate the glandular damage. We conclude that T lymphocytes are required for the adoptive transfer of specific tissue damage observed in autoimmune vesiculo‐prostatitis as well as for the development of a cell‐mediated immune response to MAG antigens. Whether the same or distinct T‐cell subsets are involved in these two effects is discussed.

Oxidative stress-related parameters in prostate of rats with experimental autoimmune prostatitis.

Oxidative stress in tissues can be provoked by an augmented metabolic rate, which may sometimes be combined with a decrease in the antioxidant capacity.

Age-related alterations in inflammatory response during experimental autoimmune prostatitis

Experimental autoimmune prostatitis (EAP) is an experimental model of autoimmune disease, developed in Wistar rats against prostatic components. The 12-and 18-month-old rats with EAP show a higher cellular autoimmune response and lower humoral autoimmune response compared to 3-month-old rats. The analysis of NO(.) and O(2)(-) production by peritoneal exudate cells (PECs) resulted in a higher NO(.) and O(2)(-) production in EAP rats at all ages, compared to control animals. PECs from 12- and 18-month-old rats produced more NO(.) and less O(2)(-) than PECs from 3-month-old rats. However, lipopolysacharide (LPS) did not stimulate PECs from aged rats for NO(.) production as much as in 3-month-old rats and thus, turning out in a lower index of LPS-stimulation of PECs from aged rats, compared to 3-month-old rats. Furthermore, the mast cells number in prostates of EAP rats, especially the number of degranulated cells, was higher than in control animals, but no significant differences were found between 3- and 12-month-old control rats. In conclusion, these results show that aging affects differentially the inflammation mediators during EAP.

TIME-COURSE STUDY OF CELLULAR IMMUNE RESPONSE AND TESTOSTERONE METABOLISM IN AN AUTOIMMUNE MODEL FOR CHRONIC PROSTATIC INFLAMMATION

PURPOSE Little is known of the etiology and pathogenesis of chronic inflammatory prostate diseases of noninfectious origin. In our experimental autoimmune rat model for chronic prostatic inflammation (CPI) we evaluated, in a time-course study, the specific cellular immune response to male accessory glands (MAG) and metabolic activity in the prostate gland. Results obtained in CPI rats were compared with data from rats immunized with kidney homogenate as well as from non-treated rats. MATERIALS AND METHODS Specific cellular immune response against MAG antigen(s) was studied by delayed type hypersensitivity (DTH) and lymphocyte proliferation tests. The prostate 5alpha-reductase activity was studied in prostate homogenates by thin layer chromatography (TLC). RESULTS DTH values were positive in MAG treated rats sacrificed at days 7 and 28 after first immunization (FI) (p < or = 0.05) in relation to kidney treated and non-treated rats. When we analyzed the proliferative responses to MAG antigen(s), an antigen specific proliferation, as shown by the mean [3H]thymidine uptake (cpm), was observed in rats sacrificed on days 14 and 28 (p < or = 0.05) after FI. The metabolic studies indicated that the 5alpha-reductase activity decreased slightly in MAG treated groups at day 14 after FI and diminished significantly at the end of CPI development. CONCLUSION These data reveal that the prostatic endocrine cell destruction during CPI could be a consequence of immune/inflammatory cell mediated processes.

Relationship between immune state and tumor growth rate in rats bearing progressive and non-progressive mammary tumors.

Abstract Impaired immune responses occur frequently in cancer patients or in tumor-bearing animals, but the mechanisms of the tumor-induced immune defects remain poorly understood. The aim of the present study was to determine the relevance of the immune system in the control of tumor growth. We have developed a model of progressive and non-progressive mammary tumor, chemically induced in female Wistar rats. In this model we evaluated the development of an immune response after immunization of rats bearing progressive and non-progressive tumors with a non-related antigen, such as sheep red blood cells. We also studied the activation state of peritoneal macrophages from animals bearing tumors by evaluating the production of free radicals. Our findings indicated that the cell-mediated immunity in rats bearing progressive tumors fails to respond to heterologous antigen in vivo, as demonstrated by a negative delayed-type hypersensitivity reaction, and is accompanied by minor nitric oxide production by peritoneal exudate cells as well as a lower capacity for macrophage activation. The study of non-progressive tumor-bearing rats indicated that the cell-mediated immune response was intact and an activated state of macrophages was found in vivo. The results described in this paper should be taken into account when therapies based on cancer vaccines are chosen for the treatment of cancer.

EXPERIMENTAL AUTOIMMUNE PROSTATITIS (EAP): ENHANCED RELEASE OF REACTIVE OXYGEN INTERMEDIATES (ROI) IN PERITONEAL MACROPHAGES

The metabolic state of peritoneal macrophages is defined quantitatively for spontaneous ROI release and compared with those produced after cell contact with phorbol myristate acetate (PMA) or zymosan (OZ) particles. Peritoneal exudate cells (PEC) from EAP animals spontaneously released significantly more ROI than cells from controls rats, indicating that mononuclear phagocytes from autoimmune rats were more activated than populations cells arising from rats injected with BSA, with CFA or non-injected. These findings could indicate an in vivo activation state in PEC from autoimmune rats different from that obtained with heterologous antigens or CFA immunization procedures. The release of ROI induced after in vitro stimulus was, in general, higher in cells from autoimmune than in BSA or CFA treated rats. This differential responsiveness between the MAG, BSA and CFA injected macrophage populations could indicate that during the autoimmune process the autoantigen/s could amplify the inflammatory response triggered by them. Although release of oxygen metabolites represents only one of many potential mechanisms of tissue injury, this together with the lesions observed in the prostate gland indicate that oxygen radicals could be involved in this autoimmune disease.

Effect of estrogen and antiestrogen therapy in rats bearing mesenchymal tumors.

We applied both hormonal and antiestrogen treatment in female Wistar rats to analyze the estrogen dependence of the growth of sarcomas induced with 9,10-dimethyl-1,2-benzanthracene. Animals bearing tumors of 10 mm in diameter were divided at random into five groups and submitted to different treatments during 24 weeks. The treatment with ovariectomy and tamoxifen in tumor-bearing animals resulted in tumor growth suppression and prolonged survival by a protection against the lethal tumor. On the other hand, the estrogen treatment exerted an adverse effect showing a faster growth of the tumors and a great decrease in survival. In summary, the antiestrogen treatment can have an antitumor effect in mesenchymal tumors, possibly by modifying the immunological status of the host.

DNA antibodies detected by microhemagglutination test in the diagnosis of systemic lupus erythematosus.

A method of tanned erythrocyte agglutination of wide applicability is described for the study of DNA antibodies. The practical aspects of the method have been explored in estimation of antibodies to DNA in human cases of systemic lupus erythematosus, discoid lupus erythematosus, rheumatoid arthritis, other collagenoses and not related diseases. This method was found to be of high sensitivity and specificity, detecting DNA antibodies only in sera of systemic lupus erythematosus. Results were compared with those obtained by immunofluorescence test using rat liver hepatocytes as source of nuclei.