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 male accessory glands autoaggression on androgenic cytosolic and nuclear receptors of rat prostate.

The effect of immunization against male accessory gland (MAG) homogenates over androgenic cytosolic and nuclear receptors of rat prostate was studied. In the MAG-immunized rats the Bmax of cytosolic receptors was significantly increased (120.3 +/- 44.3 vs 47.7 +/- 24.9 fmol/mg protein, p less than 0.01, mean +/- SD). In contrast, the Bmax of nuclear receptors in the MAG-immunized rats showed no significant difference as regarded controls (kidney immunized rats) when expressed as fmol/100 micrograms DNA (196.1 +/- 84.8 vs 148.3 +/- 88.9) but it show to slight differences (p less than 0.1) when data were reported as percent of weight of tissue (2,189 +/- 918.6 vs 1,303 +/- 611.2 fmol/g wet issue). Results (mean +/- SD) on binding affinity of cytosolic receptors showed no significant differences in MAG-immunized rats as compared with controls (Kd: 1.98 +/- 0.66 vs 1.92 +/- 0.20 nM). Likewise, only a slight difference between both groups was attained for Kds of nuclear receptors (2.34 +/- 0.28 vs 1.80 +/- 0.62 nM, p less than 0.2). On the other hand, 5 alpha 1-dihydrotestosterone (DHT) values obtained in prostate homogenates were significantly decreased in MAG-immunized rats as compared with controls (17.4 +/- 2.0 vs 7.1 +/- 0.9 ng/g tissue, mean +/- SD, p less than 0.01). However, testosterone (T) levels in gland tissue showed no significant differences between both groups (2.4 +/- 0.5 vs 2.6 +/- 0.3 ng/g tissue) with an increase in the T: DHT ratio from 0.14 to 0.37.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of cytotoxic cells by syngeneic prostate antigens in experimental autoimmune vesiculo-prostatitis.

In our experimental model of autoimmune vesiculo-prostatitis, obtained by immunization with syngeneic male accessory glands (MAG) and complete Freund's adjuvant, the presence of specific autoreactive cells with cytotoxic activity against prostate antigens was studied. The specific cytotoxicity generated in MAG immunized rats was tested using 51Cr labelled syngeneic prostate cells or labelled chicken erythrocytes coated with specific antigens (MAG homogenate or chromatographic fractions from prostate homogenate) which were used as target cells in a medium free of complement. The addition of spleen sensitized cells to prostate cells suspension produced a significant release of 51Cr in regard to normal effector cells (11.87 +/- SE 1.12 versus 1.5 +/- 0.75). Similar results were obtained when MAG-coated erythrocytes were used as target cells (10.87 +/- SE 0.62 versus 1.50 +/- 0.25). Depletion of T but no B or adherent-cells was shown to abolish the lytic effect indicating that MAG immunization provides determinants which are recognized by sensitized T-cells on cells of the prostate gland where the most severe tissue alterations were previously observed. Erythrocytes coated with chromatographic fractions obtained from prostate homogenate were used to identify the antigens triggering the lytic effect. It was demonstrated that two fractions (FI and FII) functioned as in vivo sensitizing antigens as well as in vitro activating antigens for themselves. The restimulation in vitro of sensitized cells with purified prostate fractions induces an additional lytic effect suggesting that an expansion of effector cells may take place after contacting the antigens at the prostate site.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoinmunidad experimental contra glandulas sexuales accesorias masculinas de rata: correlación entre lesion tisular especifica y reactividad de linfocitos de timo, medula osea, bazo, ganglios y sangre / Experimental autoimmunity against male accessory glands of rats: correlation between specific tissular lesion and lymphocyte reactivity of thymus, bone marrospleen, ganglia and blood

En el modelo experimental de vesículoprostatitis autoimune logrado por isoinmunización de ratas con homogenato de glándulas sexualess accesorias masculinas (GAM-R) y coadyuvante de Freund completo (CFC) se estudió la respuesta de anticuerpos hemaglutinantes, precipitantes y fijadores de complemento. Tambíen se analizó la respuesta imune mediada por células (IMC) en órganos inmunnocompetentes (OIC) primarios (médula ósea timo), OIC secundarios (bazo, ganglios linfáticos) y en circulación mediante cultivo de linfocitos, inhibición de la migración de macrófagos (MIF) indirecta y factor reactivo de piel (SRF), incluyéndose también la detección de reacciones de hipersensibilidad cutánea demorada (HCD) en ratas inmunes a GAM-R y en controles tratados con CFC o con glándulas sexuales accesorias de conejo (GAM-C) y CFC. Asimismo, estudios histológicos y demicroscopía electrónica permitieron establecer las características de las alteraciones hísticas inducidas en las glándulas objetivo. En 16 de 22 ratas inmunizadas con GAM-R se observó infiltrado de células mononucleares principalmente en intersticio de próstata y vesícula seminal. A nivel ultraestructural se observaron alteraciones en células epiteliais y linfocitos infiltrado el tejido epitelial. El análisis de la correlación entre alteraciones tisulares específicas y presencia de anticuerpos circulantes, demostró que en 13 de 16 animales con daño tisular evidente, la búsqueda de respuesta inmune humoral resultó negativa. Por el contrario, la respuesta IMC fue demostrada en todos ellos con alto grado de activación, ya que varios factores que median la inmunidad celular fueron detectados. Estos resultados y las características histopatológicas de las glándulas objetivo sugiere que un mecanismo efector mediado por células conduce al daño tisular. El número de factores mediadores detectados en los diferentes sectores (central y periférico) se consideró índice de expansión y activación de la respuesta IMC. Su correlación con los estudios histológicos demostró que en el grupos con histología negativa las células inmunococmpetentes de OIC primarios no revelan respuesta IMC o responden débilmente en el 67% de los casos, mientras que la respuesta en OIC secundarias y en circulación presenta un buen nivel de activación, ya que en el 100% de los casos 2 o más factores fueron detectados...

Autoinmunidad experimental contra glandulas sexuales accesorias masculinas de rata: correlación entre lesion tisular especifica y reactividad de linfocitos de timo, medula osea, bazo, ganglios y sangre / Experimental autoimmunity against male accessory glands of rats: correlation between specific tissular lesion and lymphocyte reactivity of thymus, bone marrospleen, ganglia and blood

En el modelo experimental de vesículoprostatitis autoimune logrado por isoinmunización de ratas con homogenato de glándulas sexualess accesorias masculinas (GAM-R) y coadyuvante de Freund completo (CFC) se estudió la respuesta de anticuerpos hemaglutinantes, precipitantes y fijadores de complemento. Tambíen se analizó la respuesta imune mediada por células (IMC) en órganos inmunnocompetentes (OIC) primarios (médula ósea timo), OIC secundarios (bazo, ganglios linfáticos) y en circulación mediante cultivo de linfocitos, inhibición de la migración de macrófagos (MIF) indirecta y factor reactivo de piel (SRF), incluyéndose también la detección de reacciones de hipersensibilidad cutánea demorada (HCD) en ratas inmunes a GAM-R y en controles tratados con CFC o con glándulas sexuales accesorias de conejo (GAM-C) y CFC. Asimismo, estudios histológicos y demicroscopía electrónica permitieron establecer las características de las alteraciones hísticas inducidas en las glándulas objetivo. En 16 de 22 ratas inmunizadas con GAM-R se observó infiltrado de células mononucleares principalmente en intersticio de próstata y vesícula seminal. A nivel ultraestructural se observaron alteraciones en células epiteliais y linfocitos infiltrado el tejido epitelial. El análisis de la correlación entre alteraciones tisulares específicas y presencia de anticuerpos circulantes, demostró que en 13 de 16 animales con daño tisular evidente, la búsqueda de respuesta inmune humoral resultó negativa. Por el contrario, la respuesta IMC fue demostrada en todos ellos con alto grado de activación, ya que varios factores que median la inmunidad celular fueron detectados. Estos resultados y las características histopatológicas de las glándulas objetivo sugiere que un mecanismo efector mediado por células conduce al daño tisular. El número de factores mediadores detectados en los diferentes sectores (central y periférico) se consideró índice de expansión y activación de la respuesta IMC. Su correlación con los estudios histológicos demostró que en el grupos con histología negativa las células inmunococmpetentes de OIC primarios no revelan respuesta IMC o responden débilmente en el 67% de los casos, mientras que la respuesta en OIC secundarias y en circulación presenta un buen nivel de activación, ya que en el 100% de los casos 2 o más factores fueron detectados...(AU)

Experimental autoimmunity to rat male accessory glands (MAG): circulating antibodies, immunoglobulins bound to target glands, and immunoglobulins-secreting cells.

A correlation between spleen B-cell antibody production against MAG antigens and the presence of different antibodies in circulation or antibodies bound to target glands was attempted. The number of 7S and 19S Ig-secreting cells (ISC) found in the spleen and the number of ISC generated after in vitro stimulation of the cells with MAG antigens were evaluated by using the hemolytic plaque assay. Low numbers of 7S and 19S ISC--less than 0.01% of spleen cells--were generated in response to MAG immunization, and no significative increase was observed after in vitro culture of spleen cells with MAG antigens, suggesting that secretory activity of the B-cells can not be improved when liberated from humoral homeostatic mechanisms. The humoral response of MAG-immunized rats, investigated by complement fixation and immunodiffusion assays, has proved negative, and in only two out of 17 rats a weak haemagglutinating activity was observed. Attempts to detect antibodies bound to cellular MAG antigens by immunofluorescence have shown a weak fluorescence in the epithelial cells of the prostate gland in only two rats. In both cases a concomitant tissue damage was observed, but in nine out of 11 cases with histological alterations no fluorescence was observed in the target glands. The medium value of rosette-forming cells (RFC) found in the spleen of MAG-immunized rats did not significantly differ from the value of the HSA-treated control group, although both groups differ in their specific humoral response.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental autoimmune damage to rat male accessory glands. I. Transfer of autoimmune response by spleen cells.

Spleen cells obtained 30 days after the first immunization of rats isoimmunized with an extract of male accessory glands (MAG) were capable of adoptively transferring specific cell-mediated immunity to normal syngenic recipients. Humoral and cell-mediated immune responses were investigated in donor and in the recipient rats that were killed 7 days after intravenous (IV) injection of the cells. In recipient rats the cell-mediated immunity showed multiple ways of expression and in some cases this was exemplified by a sharp increase in regard to the donor's response. Furthermore, a widespread reactivity in the spleen, lymph nodes, and thymus cells was detected. On the contrary, no circulating antibodies to MAG antigens were demonstrated after the spleen cell transfer. Cell separation studies showed that a nylon wool-nonadherent cell was responsible for the transfer of the cell-mediated immune response. This was abrogated by depletion of T lymphocytes and treatment with antirat thymocytes serum and complement. The mechanism of transfer and development of the cell-mediated immunity in recipient rats is discussed.

Experimental autoimmune damage to rat male accessory glands. II. T cell requirement in adoptive transfer of specific tissue damage.

Experimental autoimmune vesiculo-prostatitis (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.

Immunocompetence and its modification after BCG immunotherapy in patients with colon carcinoma.

The ability to develop cutaneous response to Mantoux, phytohemagglutinin (PHA) and dinitrochlorobenzene (DNCB) was studied in patients with carcinomas in the digestive tract, with particular emphasis on cancer of the colon, in patients with benign pathology and in a control group. The patients with a malignant disease in the digestive tract, considered as a group, showed a remarkable decrease of responses to Mantoux (31%), to PHA (21%) and to DNCB (58%) compared to the control group where incidence amounted to 61%, 73% and 100% respectively. The depression in the immune cellular response is more remarkable yet in colon carcinoma (Mantoux 11%, PHA 0%, DNCB 11%) all of which suggest that the impairment of the immune response depends on the tumor localization. An increase of unresponsiveness was also observed within the group with a benign pathology although the deterioration is lower than that observed in the malignant group. The patients with adenocarcinoma of the colon received BCG immunotherapy and the changes in cellular and humoral response were studied in them. Although the improving mechanism does not seem to affect simultaneously the various expressions of cell mediated immunity, a stimulating effect in the response was observed in what refers to recall antigen, inflammatory reaction and sensitization to DNCB. These changes ranked Mantoux greater than DNCB greater than PHA. There was a direct correlation between skin test reactivity to at least one antigen and the patient survival, but is not the case with the changes observed in the immunoglobulins level. The significance of these changes in relation to the possible anti-tumor effect is discussed.

Immunocompetence and its modification after BCG immunotherapy in patients with colon carcinoma

The ability to develop cutaneous response to Mantoux, phytohemagglutinin (PHA) and dinitrochlorobenzene (DNCB) was studied in patients with carcinomas in the digestive tract, with particular emphasis on cancer of the colon, in patients with benign pathology and in a control group. The patients with a malignant disease in the digestive tract, considered as a group, showed a remarkable decrease of responses to Mantoux (31

), to PHA (21

) and to DNCB (58

) compared to the control group where incidence amounted to 61

respectively. The depression in the immune cellular response is more remarkable yet in colon carcinoma (Mantoux 11

) all of which suggest that the impairment of the immune response depends on the tumor localization. An increase of unresponsiveness was also observed within the group with a benign pathology although the deterioration is lower than that observed in the malignant group. The patients with adenocarcinoma of the colon received BCG immunotherapy and the changes in cellular and humoral response were studied in them. Although the improving mechanism does not seem to affect simultaneously the various expressions of cell mediated immunity, a stimulating effect in the response was observed in what refers to recall antigen, inflammatory reaction and sensitization to DNCB. These changes ranked Mantoux greater than DNCB greater than PHA. There was a direct correlation between skin test reactivity to at least one antigen and the patient survival, but is not the case with the changes observed in the immunoglobulins level. The significance of these changes in relation to the possible anti-tumor effect is discussed.

Immunocompetence and its modification after BCG immunotherapy in patients with colon carcinoma.

The ability to develop cutaneous response to Mantoux, phytohemagglutinin (PHA) and dinitrochlorobenzene (DNCB) was studied in patients with carcinomas in the digestive tract, with particular emphasis on cancer of the colon, in patients with benign pathology and in a control group. The patients with a malignant disease in the digestive tract, considered as a group, showed a remarkable decrease of responses to Mantoux (31

), to PHA (21

) and to DNCB (58

) compared to the control group where incidence amounted to 61

, 73

and 100

respectively. The depression in the immune cellular response is more remarkable yet in colon carcinoma (Mantoux 11

, PHA 0

, DNCB 11

) all of which suggest that the impairment of the immune response depends on the tumor localization. An increase of unresponsiveness was also observed within the group with a benign pathology although the deterioration is lower than that observed in the malignant group. The patients with adenocarcinoma of the colon received BCG immunotherapy and the changes in cellular and humoral response were studied in them. Although the improving mechanism does not seem to affect simultaneously the various expressions of cell mediated immunity, a stimulating effect in the response was observed in what refers to recall antigen, inflammatory reaction and sensitization to DNCB. These changes ranked Mantoux greater than DNCB greater than PHA. There was a direct correlation between skin test reactivity to at least one antigen and the patient survival, but is not the case with the changes observed in the immunoglobulins level. The significance of these changes in relation to the possible anti-tumor effect is discussed.