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M B Parr

Publications and source records attributed to M B Parr.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ultrastructure and morphometry of the urethral glands in normal, castrated, and testosterone-treated castrated male mice.

Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly arranged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone.

Animals↗
PubMed1992

Urethral glands of the male mouse contain secretory component and immunoglobulin A plasma cells and are targets of testosterone.

The occurrence and possible functions of mucosal immunity in the male urogenital tract have not been extensively investigated. In this study we used immunolabeling to localize secretory component (SC) and immunoglobulin (Ig) A in the urogenital tract of the male mouse. SC was located in the ventral prostate, while SC and IgA plasma cells were both detected in the urethral glands in the pelvic and bulbous portions of the urethra. SC and IgA were not observed elsewhere in the urogenital tract. We also examined the ventral prostate and urethral glands of sham-castrated, oil-treated castrated, and testosterone-treated castrated mice. There was a striking reduction in the size of the ventral prostate and urethral glands in oil-treated castrates compared to the other two groups, based on gross and histological morphology. Morphometric analysis showed that the cell and nuclear sizes of the urethral gland acinar cells were reduced after castration and restored to normal size by testosterone treatment. Androgen receptors (AR) were localized in the nuclei of urethral gland cells by immunocytochemistry using anti-AR antibodies. Labeling of SC and IgA plasma cells was similar in the urethral glands and ventral prostates of sham- and testosterone-treated castrates, but was reduced or absent at these sites in oil-treated castrates. These studies show that the ventral prostate and urethral glands may be sites for secretory immunity in the male murine urogenital tract, and that the urethral glands are targets for testosterone.

Animals↗
PubMed1991

Perforin-expressing granulated metrial gland cells in murine deciduoma.

It has previously been shown that granulated metrial gland (GMG) cells of the pregnant uterus express abundant quantities of the lymphocyte pore-forming protein, perforin. No perforin was present before implantation of the embryo, but large numbers of perforin-producing GMG cells were observed after implantation, which coincides with decidualization of the uterus. The possible source of the activation factors responsible for perforin gene induction in GMG cells was studied here with the pseudopregnancy model, in which cervical stimulation of mice during estrus leads to a series of hormonal changes resembling those seen in pregnancy, but in the absence of an embryo. Subsequent stimulation of the uterus of pseudopregnant mice with oil causes the stimulated portion of the endometrium to differentiate into decidual tissue. Perforin-containing GMG cells were in fact present in the deciduomata, but not in adjacent nondecidualized tissues of the same mice. These results suggest that maternal factors associated with decidual tissue are responsible for the local expression of perforin in GMG cells.

Animals↗
PubMed1991

Secretory immune responses in the mouse vagina after parenteral or intravaginal immunization with an immunostimulating complex (ISCOM).

Immunostimulating complexes (ISCOMs) are subunit vaccines that are particularly effective in producing immunity against systemic viral infections, but their effectiveness against mucosal infections has received little attention. To study their ability to produce mucosal immune responses in the female reproductive tract, a model ISCOM was prepared containing sheep erythrocyte membrane proteins, and anti-erythrocyte IgA and IgG titres in mouse vaginal washings were measured after immunization at parenteral or local mucosal sites. The ISCOM was prepared by a modified procedure that resulted in incorporation of 10-15% of initial membrane protein compared with 1-5% previously reported. Electrophoretic analysis demonstrated that four out of five erythrocyte membrane proteins were incorporated into the ISCOM, and electron microscopic observations indicated that the ISCOM had a cage-like structure with a diameter of 40 nm, similar to previous ISCOMs. Immunization in the pelvic presacral space (p.s.-p.s.) stimulated significantly higher anti-erythrocyte IgA titres in vaginal fluid than were produced by intraperitoneal (i.p.-i.p.), subcutaneous (s.c.-s.c.), intravaginal (i.vag.-i.vag.), or i.p.-i.vag. immunizations with the same vaccine. Specific IgG titres were less dependent on the route of immunization, with p.s.-p.s., i.p.-i.p. and s.c.-s.c. administration all giving similar high titres while i.p.-i.vag. treatment induced lower titres. These observations using a model ISCOM indicate that mucosal immune responses against membrane proteins were elicited in the female reproductive tract, and that non-mucosal immunization in the pelvis was a more effective route of administration than local application of the ISCOM to the vaginal mucosa.

Adjuvants, Immunologic↗
PubMed1991

Langerhans cells and T lymphocyte subsets in the murine vagina and cervix.

Immunization in the vagina can lead to the production of specific antibodies in the luminal fluid of this organ. To help understand the immune mechanisms involved in this process, we have studied the occurrence of Langerhans cells (LCs), macrophages, natural killer cells, and T and B lymphocytes in the murine vagina and cervix during the estrous cycle. LCs in the epithelia expressed Ia, F4/80, NLDC-145, and CD45, but not Mac-1, Moma-1, and Moma-2; double-labeling demonstrated phenotypic heterogeneity in this population Ia+, NLDC-145+; Ia+, NLDC-145-; Ia+, F4/80+; Ia+, F4/80-; Ia- F4/80+. T lymphocytes of both helper and cytotoxic/suppressor types were also present in the epithelia, sometimes in close association with LCs, but natural killer cells were not observed. The stroma of the vagina and cervix contained LCs (or interdigitating cells) and macrophages but few T lymphocytes and no B lymphocytes, natural killer cells, or lymphoid nodules. These observations confirm and extend previous reports that the murine vagina and cervix contain epithelial LCs and T lymphocytes and support the suggestion that antigens in the vagina and cervix, as in the epidermis, may be recognized and presented to the immune system by epithelial LCs. However, the paucity of T cells and the absence of B cells and lymphoid nodules from the stroma suggest that antigen presentation may not occur locally but at another site such as in the draining lymph nodes.

Animals↗
PubMed1991

Mouse granulated metrial gland cells originate by local activation of uterine natural killer lymphocytes.

Natural killer (NK) lymphocytes were identified in the mouse uterus by immunostaining their surface membrane marker, LGL-1. The cells were present in large numbers from before mating through Day 14 of pregnancy. Double immunostaining indicated that uterine NK cells began to contain the pore-forming protein, perforin, on Day 6 of pregnancy in mesometrial decidua. Perforin is a probable mediator of cellular cytotoxicity found in lymphokine-activated NK and cytotoxic T lymphocytes. Activation of NK cells to produce perforin continued in mesometrial decidua on Days 8 and 10 of pregnancy and in the peripheral portion of metrial glands (MGs) on Days 12 and 14 of pregnancy, where cells at 3 stages of activation were simultaneously present: small cells with bright surface membrane staining of LGL-1 but no perforin (nonactivated), larger cells with intermediate staining of both markers (partially activated), and large cells with bright staining of perforin but no LGL-1 (fully activated). These observations indicate that activation of uterine NK cells involves loss of membrane LGL-1 as perforin accumulates in the cytoplasm, that the zone of activation shifts from mesometrial decidua to the MG on about Day 11 of pregnancy, and that nonactivated NK cells probably enter activation zones continuously during this period. Resting NK cells may enter activation zones by proliferation and/or migration from other regions of the uterus, rather than from blood, because depletion of circulating NK cells during pregnancy by treatment with NK-1.1 or asialo GM1 antibodies had no effect or only a small effect on the numbers of LGL-1-or perforin-positive cells seen in the uterus later in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Langerhans cells phagocytose vaginal epithelial cells undergoing apoptosis during the murine estrous cycle.

Langerhans' cells (LCs) have been studied extensively in the epidermis, where they function as antigen-presenting cells. LCs are also present in the stratified epithelia of the murine vagina and cervix, but their function at these sites is not known. Recent reports noted the association of LCs with vaginal epithelial cells undergoing apoptosis and suggested that LCs might be involved in phagocytosis of dead cells. The present study describes the ultrastructural details of this process. The results demonstrate that LCs in murine vaginal epithelium during late metestrus and early diestrus phagocytose apoptotic epithelial cells and may thereby contribute to the normal turnover of the vaginal epithelium during the estrous cycle.

Animals↗
PubMed1991

Antigen recognition in the female reproductive tract. II. Endocytosis of horseradish peroxidase by Langerhans cells in murine vaginal epithelium.

Previous studies have shown that dendritic cells in the murine vaginal epithelium at diestrus and metestrus can endocytose intravaginally administered soluble protein tracers, but the identity of the dendritic cells was not established. In the investigation reported here, we used a combination of histochemistry and transmission electron microscopy to study the endocytosis of exogenous horseradish peroxidase by vaginal dendritic cells and to identify these cells as Langerhans' cells on the basis of their cellular associations, ultrastructural morphology, and the presence of Langerhans' cell granules.

Administration, Intravaginal↗
PubMed1990

Granulated metrial gland cells of pregnant mouse uterus are natural killer-like cells that contain perforin and serine esterases.

The mouse uterus during pregnancy contains a large population of lymphoid cells termed granulated metrial gland (GMG) cells. Our observations suggest that these cells are highly activated cytolytic lymphocytes related to NK or lymphokine-activated killer cells. Immunostaining demonstrated asialo GM1 and Thy-1 on GMG cells, both of which are expressed by NK cells. Decidua basalis tissue and isolated GMG cells contained three proteins that are characteristic of activated cytolytic lymphocyte granules: perforin, serine esterase 1, and serine esterase 2. These mediators were demonstrated in GMG cells by Western blot analysis using polyclonal antisera and by Northern blot analysis using specific cDNA probes for their mRNA. The proteins were not detected in normal spleen or liver or in asialo GM1+ cells isolated from those organs, consistent with the absence of these mediators from resting cytolytic cells. The amount of perforin in GMG cells was similar to that present in cloned, IL-2-stimulated, CTL shown previously to contain a large amount of this protein. A large population of NK cells bearing the surface marker LGL-1 was demonstrated at the implantation site by labeling with monoclonal antibody 4D11, but T cells were not detected. Many LGL-1+ cells at the implantation site expressed the GMG cell markers asialo GM1, Thy-1, and perforin. Staining intensities were inversely correlated, with LGL-1-bright cells showing little or no staining of GMG cell markers and LGL-1-faint cells showing more obvious staining of GMG cell markers. This suggests that LGL-1+ NK cells may differentiate in situ to GMG cells, losing LGL-1 and gaining a high concentration of GMG cell markers in the process. Activated cytolytic cells related to NK or lymphokine-activated killer cells may function in the pregnant rodent uterus to intercept and kill aberrant placental or embryonic cells that might otherwise enter the female and proliferate.

Animals↗
PubMed1990

The effect of adjuvants on antibody titers in mouse vaginal fluid after intravaginal immunization.

Intravaginal (ivag) immunization elicits secretory immune responses in the female reproductive tract, but little is known about the safety and effectiveness of adjuvants for such immunization. Mice were immunized intravaginally once daily for 5 days with large doses of horse ferritin combined with aluminum hydroxide (AH), muramyl dipeptide (MDP), monophosphoryl lipid A (MPL), dimethyl dioctadecyl ammonium bromide (DDA) or cholera toxin (CT). Titers of anti-ferritin IgA and IgG were measured in vaginal fluid by ELISA. The most effective adjuvant for ivag primary immunization was AH, while MPL was most effective for ivag boosting. None of the adjuvants caused a detectable tissue reaction in vaginal mucosa. Primary ivag immunization for 5 days with ferritin and AH followed by ivag boosting for 5 days with ferritin and MPL elicited higher IgA titers in vaginal fluid than systemic priming and boosting with ferritin and AH or systemic priming and ivag boosting with ferritin and MPL. Systemically immunized animals exhibited the highest IgG titers in vaginal fluid. The data indicate that adjuvants, particularly AH, can increase local immune responses to intravaginal immunization, but it should be noted that multiple applications of large doses of antigen were used and that this route of sensitization may be relatively inefficient.

Adjuvants, Immunologic↗
PubMed1990

Antigen recognition in the female reproductive tract: I. Uptake of intraluminal protein tracers in the mouse vagina.

Local immunization in the vagina of several species elicits immune responses, but little is known about the uptake, processing and recognition of antigens at this site. We investigated the uptake of intravaginally administered tracers using FITC-bovine albumin, FITC-horse ferritin and FITC-horseradish peroxidase in non-pregnant and pregnant mice. Tracers were detected in cells in the vaginal epithelium and stroma at diestrus, proestrus and metestrus, but not at estrus. During pregnancy, racers were present in vaginal cells on Day 6 but not on Day 13. The distribution of tracers in the vagina was the same in all mice. They were present in vaginal epithelium in cells similar to Langerhans' cells and in the stroma in cells that resembled dendritic cells, fibroblasts or macrophages. In some non-pregnant mice, tracers were present in cells adjacent to lymphatic nodules located in the adventitia between the vagina and urethra. Tracers were seen in phagocytic cells lining the marginal and medullary sinuses of the draining lymph nodes (iliac nodes) in some non-pregnant mice at 4 h after intravaginal administration, or in small, dendritic cells in the paracortex at 17 h. To test the possibility that transfer of proteins into the vagina was due to toxic effects of the tracers, FITC-conjugated proteins were also administered into the lumen of uterine horns, and their distribution in horns, cervix and vagina was studied. In uterine horns, tracers were either absent or were located only in apical vesicles in the luminal epithelium. Tracers were present in the cervix and vagina as described above for intravaginal tracers. This result suggests that uptake of tracers in the vagina was not due to toxic effects, and that the vagina and cervix are major sites of protein uptake into the reproductive tract.

Administration, Intravaginal↗
PubMed1990

Measurement of natural killer activity and target cell binding by mouse metrial gland cells isolated by enzymic or mechanical methods.

Cells of the metrial glands of mice were isolated by enzymic or mechanical dissociation procedures. Morphological observations indicated that up to half of the enzymically dissociated cells and nearly all of the mechanically dissociated cells were granulated metrial gland cells, but the presence of some fibroblast-like stromal cells among the latter population was not ruled out. Moreover, the granulated metrial gland cells had lost a substantial part of their granule content during isolation. Both cell preparations had little or no natural killer (NK) activity, indicating either that granulated metrial gland cells are not NK-like or that their NK activity was impaired by loss of granule-associated lytic substances or by other factors. Enzymically dissociated metrial gland cells did not bind significantly to the NK target cell YAC-1, nor did they develop granules, NK activity, or the ability to bind YAC-1 cells during culture in vitro, either in normal medium or with the addition of indomethacin or lymphokines. Mechanically dissociated metrial gland cells bound avidly to YAC-1 cells but not to P815 cells or adult thymus cells, which are not NK target cells. Since many if not most of the mechanically dissociated metrial gland cells appeared morphologically to be granulated metrial gland cells, their selective binding to an NK target cell suggests that granulated metrial gland cells may be related in some way to NK cells.

Animals↗
PubMed1990

A comparison of antibody titres in mouse uterine fluid after immunization by several routes, and the effect of the uterus on antibody titres in vaginal fluid.

Measurements of specific antibody titres in uterine fluid of mice immunized by different routes indicated that two immunizations in the pelvic presacral space using aluminium hydroxide as adjuvant was a simple and effective way to elicit a significant IgA and IgG response. Higher IgA and IgG titres were produced in uterine fluid by subcutaneous immunization with antigen in Freund's complete adjuvant followed by intravaginal boosting without adjuvant, but this immunization involved both a toxic adjuvant and repeated applications of large doses of antigen in the vagina. Intragastric immunization produced an IgA response in the uterus but no IgG. Local intravaginal priming and boosting with large doses of antigen without adjuvant produced an IgA response in uterine fluid, but was less effective for IgG and was inefficient in terms of time and the amount of antigen used. Hysterectomy reduced the concentration of specific IgA in vaginal fluid of immunized mice to no more than 5% of normal, indicating that most of the IgA in vaginal fluid originates in the uterus. In contrast, IgG titres were not significantly different in hysterectomized and intact mice. IgA titres in vaginal fluid were at least partly restored to normal levels in sham-hysterectomized mice.

Animals↗
PubMed1990

Secretory immune responses in mouse vaginal fluid after pelvic, parenteral or vaginal immunization.

Intravaginal immunization causes IgA responses in vaginal fluid, but so far lymphoid nodules in mouse vaginal mucosa have not been detected. The present study was therefore designed to test the hypothesis that IgA responses in the female reproductive tract may be generated in the regional iliac lymph nodes. Two, non-mucosal sites were identified in the female mouse pelvis, the subserous and presacral spaces, from which lymph drains mainly to the iliac nodes. Immunization at these pelvic sites with horse ferritin adsorbed to aluminum hydroxide (AH) caused much higher IgA and IgG titres in vaginal fluid than intravaginal immunization; moreover, the pelvic immunizations caused significantly higher and better sustained IgA titres in vaginal fluid than subcutaneous immunization near the scapulae or in the perineum, while IgG titres in vaginal fluid were similar in these groups. Additional mice were immunized with ferritin subcutaneously near the scapulae or in the presacral pelvic space using dimethyl dioctadecyl ammonium bromide (DDA), AH plus muramyl dipeptide, or the Ribi adjuvant system as adjuvants. Pelvic immunization caused higher IgA titres in vaginal fluid than subcutaneous immunization in each case. The IgA response stimulated by DDA was similar to that produced by AH but higher than the responses caused by the other two adjuvants, while IgG titres were similar with all four adjuvants in both sites. The results suggest that non-mucosal, pelvic immunization is particularly effective in stimulating IgA responses in the female reproductive tract. The observation is consistent with the possibility that the iliac lymph nodes may play a role in the development of IgA responses in the reproductive tract.

Adjuvants, Immunologic↗
PubMed1989

Immunohistochemical investigation of secretory component and immunoglobulin A in the genital tract of the female rat.

There was intense labelling of secretory component (sc) in the glandular and luminal epithelia of the uterine horns at pro-oestrus, oestrus and Day 1 of pregnancy, but at other stages labelling was weak or undetectable. There was also intense labelling of sc in the superficial layer of cells in the stratified epithelia of the cervix and vagina at pro-oestrus and Days 4-7 of pregnancy, but not at other stages. Plasma cells containing immunoglobulin A (IgA) were not observed in any region of the genital tract at any of the times studied. The presence of sc coupled with an absence of IgA-containing plasma cells suggest that IgA in genital tract secretions of the female rat may be derived mainly from serum.

Animals↗
PubMed1989

Immunohistochemical localization of secretory component and immunoglobulin A in the urogenital tract of the male rodent.

The mucosal immune system in the male rodent urogenital tract was studied by localizing secretory component (sc) in the rat and immunoglobulin A (IgA) in both rat and mouse by immunofluorescence. In the rat, bright labelling of sc was observed at several sites, including the ejaculatory ducts, excretory ducts of several accessory glands, and urethral glands in the pelvic and bulbous portions of the urethra. Pale labelling of sc was detected in epithelial cells of the ventral prostate gland. Plasma cells containing IgA were only observed in the urethral gland in the bulbous portion of the urethra in rats and mice. These results suggest that IgA may be transported into the urogenital tract of the male rat primarily at sites distal to the production of seminal fluid and spermatozoa. While locally synthesized IgA may be available in the bulbous urethra, it appears that serum may be the main source of IgA for transport into the rat urogenital tract at the other sites where its receptor, sc, was demonstrated.

Animals↗
PubMed1988

Endocytosis in the epithelium of the mouse oviduct.

We studied the pathway of serum protein transport into the lumen of the mouse oviduct by localizing several tracer proteins in the oviduct after intravenous injection on days 1, 5, and 11 of pregnancy. Fluorescent proteins were observed in the lamina propria and in vesicles in the lumenal epithelial cells mainly in the preampulla segment on days 5 and 11 of pregnancy. In the isthmus, there was much less fluorescence in the lamina propria and no fluorescent vesicles in lumenal epithelial cells. This is similar to previous observations on day 1 and indicates that the uptake of serum proteins into lumenal epithelial cells in the preampulla is not limited to the time when embryos are present in the oviductal lumen. Horseradish peroxidase (HRP) was present in the lamina propria of the preampulla on days 1 and 5, but direct tracer movement into the oviductal lumen was blocked by the epithelial junctional complexes. Within the epithelial cells, HRP was localized in endocytic vesicles along the basolateral membrane, multivesicular bodies (mvb), elongated dense bodies below the nucleus (bdb), and many small vesicles near the apical surface of the cells. Ferritin was also used as a tracer and was observed in the same locations as HRP. Acid phosphatase in the epithelial cells of the preampulla on day 1 was localized in mvb and bdb, indicating that these structures are lysosomes. It appeared that HRP and ferritin followed two pathways after basolateral endocytosis by the epithelial cells in the preampulla: 1) they were transported to apical vesicles that may release their contents into the oviductal lumen, or 2) they were transported to lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗