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S C Bell

Publications and source records attributed to S C Bell.

At least 163 records · Page 9Linked to original sources
PubMed1985

Immunohistochemical localization of murine alpha 1-pregnancy-associated protein (alpha 1-PAP) in non-pregnant females: a comparative study with human pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG).

A murine pregnancy-associated protein (alpha 1-PAP) was demonstrated by immunoperoxidase (PAP) staining within Ia positive cells in gut-associated lymphoid tissue and intestinal mucosae of normal female MF1 but not C57BL/10 mice. These immunohistochemical findings reflect the differences in serum alpha 1-PAP concentrations between the two strains, being 50-fold higher in the MF1 females. Staining for alpha 1-PAP was also detected within perivascular and periportal hepatocytes of MF1 mice. Using a combined indirect immunoperoxidase (PAP)/direct immunofluorescence procedure, cytoplasmic alpha 1-PAP was demonstrated in a proportion of plasma cells secreting the IgA isotype. In contrast with human pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) which was observed in the majority of IgA plasma cells within the lamina propria of human gastrointestinal mucosae, on average only 15% of IgA producers in corresponding mouse tissue were positive for alpha 1-PAP. As with the localization of alpha 2-PAG, no other classes of Ig-producing cells stained for alpha 1-PAP. These observations strengthen recent proposals that alpha 1-PAP is a murine analogue of human alpha 2-PAG, a glycoprotein with immunosuppressive properties.

Animals↗
PubMed1984

Humoral immune responses in murine pregnancy. IV. Strain dependency and alloantibody specificity.

The relationship between the ability of female inbred mice to produce an anti-paternal humoral immune response to allogeneic multiparity and the genotype of the female and male strains has been investigated. Only three, all H-2b haplotype strains, were 'responder' strains and produced anti-paternal alloantibody which did not exhibit C'-dependent cytotoxicity. 'Non-responder' strains produced no alloantibody in spite of multiple pregnancies with H-2 and non-H-2 incompatible male strains. However, even responder strains did not produce alloantibody with all incompatible male strains. The absence of a response in a responder strain mated with a male strain differing at only the H-2 locus implicated a role for non-H-2 influences. A study of the specificity of pregnancy-induced alloantibody suggested that this represented only a fraction of the total alloantibody population induced by conventional immunization in the same strain combination. It is suggested that in pregnancy only the anti-non-H-2 humoral responses remain similar to those induced by immunization, whereas anti-H-2 humoral responses are either absent or are restricted to a fraction of the total foreign H-2 specificities presented. These observations are discussed in relation to the nature of the immunogenic stimulus in pregnancy and the expression of histocompatibility antigens on the feto-placental unit.

Animals↗
PubMed1984

Identification of a murine pregnancy-associated serum protein (alpha 1-PAP) a female-specific acute-phase reactant.

A murine pregnancy-associated protein (alpha 1-PAP) with alpha 1-electrophoretic mobility and an estimated molecular weight of 150 000 was present in serum from pregnant C57BL/10 mice but could not be detected in serum of mature non-pregnant females and males. During pregnancy alpha 1-PAP was first detected on Day 7, rose to maximum levels between Days 12 and 14, and thereafter declined during the remainder of pregnancy and was undetectable by Day 8 post partum. The protein was also detected in the serum of females, but not males, subjected to an inflammatory stimulus. Examination of the alpha 1-PAP levels during an acute-phase response in females demonstrated that the protein behaved as a typical classical acute-phase reactant, although the levels were only 10% of those observed during Days 12 to 14 of pregnancy. alpha 1-PAP therefore appears to represent a hitherto undescribed female-specific acute phase reactant in the mouse.

Amyloid↗
PubMed1984

Regulation of murine alpha 1-pregnancy-associated protein by gonadal steroids during the acute-phase response.

A pregnancy-associated serum protein of the mouse (alpha 1-PAP) has recently been reported to be also synthesized by the non-pregnant female, but not the untreated male, in response to injury. The role of gonadal hormones in this phenomenon has been investigated. Ovariectomy abolished the ability of injury to induce synthesis of alpha 1-PAP. Although administration to ovariectomized animals of oestradiol alone resulted in the appearance of low concentrations of alpha 1-PAP after injury, injection of either progesterone or oestradiol plus progesterone permitted injury to induce concentrations of alpha 1-PAP similar to those observed in intact injured females. Castrated mice, like intact males, failed to produce alpha 1-PAP in response to injury, but administration of either oestradiol or oestradiol plus progesterone caused injury to induce concentrations of alpha 1-PAP similar to those in injured intact females. Administration of testosterone to intact females abolished the alpha 1-PAP response to injury and administration of oestradiol plus progesterone in intact males failed to induce the same response as in castrated males. These findings suggest that testosterone can inhibit the synthesis of alpha 1-PAP in response to injury in both sexes whereas oestradiol and progesterone exhibit different abilities in males and females to facilitate the induction of alpha 1-PAP synthesis by injury.

Animals↗
PubMed1983

Humoral immune responses in murine pregnancy. III. Relationship between anti-paternal alloantibody levels in maternal serum, placenta and fetus.

Studies have been carried out on allogeneically mated pregnant female mice to examine the relationship between the levels of anti-paternal alloantibody occurring free or as soluble immune complexes in the maternal peripheral circulation and that existing in a bound form in the placenta and free in the fetal circulation. In a 'non-responder' strain of mouse, as defined by the inability to detect anti-paternal alloantibody in the peripheral serum of multiparous allogeneically mated females, no alloantibody could be detected as soluble immune complexes, bound to the placenta or in the fetal circulation. A similar situation existed in females of a 'responder' strain during their first pregnancy and in some individuals during their second. However, in 'responder' strain females possessing alloantibody in their peripheral serum, alloantibody could be eluted from the semi-allogeneic placenta when peripheral titres exceeded 1:16, and was found in the fetal serum when they exceeded 1:128. When such females were subsequently mated syngeneically, alloantibody was detected in placental eluates only when peripheral titres exceeded 1:128-256 and in the fetal serum when they exceeded 1:16. The alloantibody eluted from placentae and that found in neonatal serum exhibited similar isotype distribution to that in the peripheral serum. These results are discussed with reference to the relative importance of the yolk sac and the immunoabsorbent semi-allogeneic placenta in the restricted transfer of pregnancy-induced anti-paternal alloantibody to the fetus.

Animals↗
PubMed1983

Immunoregulatory activity of supernatants from short-term cultures of mouse decidual tissue.

Supernatants from short-term in-vitro cultures of decidual tissue, obtained from the uteri of pregnant mice from Days 4 to 13 post coitum (Day 1 = day of mating), were assessed for immunoregulatory activity by their addition to a mixed lymphocyte reaction (MLR), an in-vitro analogue of the afferent arm of the immune response. All culture supernatants tested possessed inhibitory activity in the MLR, although the extent of inhibition was affected by seeding density, length of culture, and the day of pregnancy from which decidual tissue was obtained. Inhibitory activity produced by decidual cultures increased from Day 4 to reach a maximum on Day 8, and then declined to Day 11. Two morphologically distinct cell types were present in all decidual cultures; flat dendritic cells, considered to represent decidual cells, and small round cells, but whether immunoregulatory factors are associated with both is uncertain. The results suggest that decidual tissue could fulfil a role in the local partial blockade of the afferent arm of the maternal immune response during pregnancy.

Animals↗
PubMed1983

Fetal histocompatibility antigens and maternal immune responses.

Information on the antigenic status of the fetus and placenta and the nature of the maternal alloimmune responses in pregnancy is essential for an understanding of the factors responsible for the survival of the fetus as an intrauterine allograft. Although minor histocompatibility antigens are expressed from the earliest stages of preimplantation embryonic development in the mouse the paternally inherited Class I antigens of the major histocompatibility complex are absent from both fetal and surrounding trophoblastic tissues until the mid-gestation period. In the definitive placenta, the spongiotrophoblast, a major subpopulation of trophoblast in direct contact with maternal blood and uterine tissue, expresses these MHC antigens and is potentially susceptible to immune attack. The maternal alloimmune response is extremely restricted. Antibody is detectable only in females of an H-2b haplotype, only after a second allogeneic mating, and exhibits little or no complement-fixing activity, There is no detectable generation of cytotoxic T cells. Placental and fetal tissue inoculation experiments indicate that the deviated response in pregnancy is mediated at the placental level. The failure of an experimentally induced state of hyperimmunity to prejudice the course of pregnancy is considered to be due to the immunoregulatory effect of non-antigen-specific maternal serum factors.

Animals↗
PubMed1983

Acute phase serum proteins in syngeneic and allogeneic mouse pregnancy.

The levels of two murine acute phase proteins, serum amyloid P component (SAP) and haptoglobin, have been measured in the serum of C57BL/10 female mice during syngeneic and allogeneic pregnancy. Both syngeneic and allogeneic pregnancy resulted in alterations in the levels of these proteins as compared to those observed in virgin females. Syngeneic mating resulted in an increase in concentration of both proteins during the final 3 days of pregnancy. During allogeneic pregnancy, SAP levels, after a transient increase on day 4, rose from days 6-8 and, after remaining relatively stable, increased from day 12 to reach maximum levels on day 18 of pregnancy. Levels fell dramatically during the immediate post-partum period. In contrast, although levels of haptoglobin also increased from days 6-8, for the remainder of pregnancy these increased levels remained stable. The implications of these findings are discussed in relation to the mechanisms of regulation of acute phase reactants and the immunological relationship between the mother and fetus.

Amyloid↗
PubMed1982

Glycogen-induced intrauterine leucocytosis and its effect in mouse blastocyst implantation in vivo and in vitro.

Intrauterine instillation of heat-deaggregated glycogen in virgin mice induced a marked but transient luminal infiltration of polymorphonuclear leukocytes (PMNL). Similar injections of glycogen 2 days post coitum resulted in termination of pregnancy in the majority of treated females. Embryos recovered on Day 4 of pregnancy from the glycogen-treated females, before the expected time of implantation, had developed to the cavitated blastocyst stage, and were capable of undergoing characteristic outgrowth when cultured in vitro. A small proportion, however, appeared abnormal and did not develop in vitro. Cavitated blastocysts obtained from control mated females did not undergo outgrowth in vitro in the presence of intact PMNL, homogenates of these cells or a low molecular weight (less than 1500) fraction of the homogenates and after culture appeared similar to the abnormal blastocysts recovered from glycogen-treated uteri. It is proposed that the anti-fertility effect of PMNL infiltrates is due to a low molecular weight component of these cells which acts in utero and is cytotoxic to preimplantation blastocysts before their hatching from the zona pellucida.

Animals↗
PubMed1982

Humoral immune responses in murine pregnancy. II. Kinetics and nature of the response in females preimmunized against paternal alloantigens.

The kinetics of anti-paternal alloantibody production in syngeneically and allogeneically mated mice previously immunized with allogenic spleen cells has been investigated. In allogeneically mated females, total and cytotoxic alloantibody levels increased during the final 3 days of pregnancy to reach maximal levels around 1 week after parturition. The properties of this alloantibody were indistinguishable from those of alloantibody induced by conventional immunization procedures. In syngeneically mated females no increase was observed. Total hysterectomy demonstrated that the immunogenicity of the conceptus required to produce a secondary humoral immune response was initiated in the majority of females between days 9 and 10 of pregnancy, and that the antigenic exposure by day 10 was sufficient to induce a maximal secondary response. These observations were consistent with the time of appearance of serologically demonstrable H-2 antigens on embryonic cells during pregnancy. These phenomena occurred in 'responder' and 'non-responder' female strains (referring to the ability of allogeneically mated females to produce anti-paternal alloantibody during normal pregnancy) demonstrating that they do not differ in their ability to produce a secondary immune response to alloantigens presented via the intrauterine route. The findings are discussed in relation to the nature of the immunogenic stimulus from the concepts in this system and during pregnancy.

Animals↗
PubMed1981

Humoral immune responses in murine pregnancy. I. Anti-paternal alloantibody levels in maternal serum.

The kinetics and properties of anti-paternal alloantibody produced by female C57BL(H-2b) mice in response to mating with CBA(H-2k) males have been investigated using an immunobead adsorption assay. No alloantibody was ever detected in the first pregnancy or post-partum period. 72% of females exhibited a humoral response in their second pregnancy, detectable from day 16 or 17 post-coitum, and almost all females responded in their third pregnancy. Column chromatographic and immunoelectrophoretic analysis showed that the alloantibody was IgG. Although passive transfer experiments suggested similar stability characteristics to those of cytotoxic antibody induced by experimental hyperimmunization, the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. The findings are discussed in relation to the nature of the immunogenic stimulus from the conceptus and the regulation and possible function of the humoral immune response in allogeneic pregnancy.

Animals↗
PubMed1981

Inhibitory activity of supernatants from murine decidual cell cultures on the mixed lymphocyte reaction.

Supernatants from in vitro decidual cell cultures derived from uterine cells of C57BL mice were assessed for immunoregulatory activity by addition at the initiation of a mixed lymphocyte reaction (MLR) between C57BL responder and Balb/c stimulator splenocytes. MLR inhibitory factors were present during two phases of the culture; firstly during decidual cells differentiation and secondly during involution of the culture. These factors were produced whether the cultures were derived from syngeneically or allogeneically mated mice. Addition of supernatants 24 h after the initiation of the MLR also produced an inhibitory effect. Throughout the culture period supernatants also inhibited the control MLR containing C57BL responder and stimulator splenocytes. Peaks of inhibitory material were associated with both high (greater than 1 500) and low (less than 1 500) molecular weight fractions as assessed by Sephadex G15 fractionation. No inhibitory factors were identified in supernatants from similar cultures of embryonic fibroblasts. The results are discussed with respect to the mode of action of these factors and their possible role in the maintenance of the foetal allograft.

Animals↗
PubMed1981

Differentiation of decidual cells in mouse endometrial cell cultures.

Mouse uterine cells were obtained by trypsinization of uteri at timed intervals after the induction of a decidual reaction by intraluminal instillation of arachis oil on Day 4 of normal pregnancy. Cells were also obtained from ovariectomized mouse uteri, some of which had received a progesterone-oestradiol sequence to sensitize the uterus to a decidual stimulus. The differentiation of decidual cells was followed in cultures of these cells. The morphology of the cells obtained after 6 days in culture was dependent upon the seeding density employed. At low seeding density (plating densities of 75-100 cells/mm2) no net increase in cell number was observed, but large mononucleated stellate cells were present, with cytoplasmic and nuclear areas increased by 4-fold. At higher seeding densities (plating densities of up to 709 cells/mm2), a prolongation of cell survival and the appearance of substantial numbers of binucleated cells were observed. However, both cell types were characterized by the accumulation of filamentous material in the cytoplasm. Even at optimal seeding density the life-span of the decidualized cells could not be prolonged beyond 9 days. Uterine cells from hormone-treated ovariectomized animals underwent similar transformations but those from untreated ovariectomized mice gave only isolated islets of epithelial cells and scattered fibroblast-like cells in culture. These observations suggest that discrepancies in previous reports of in-vitro deciudualization of rat uterine cells result from differences in the seeding densities employed.

Animals↗