Suppression of Lymphocyte Activation by a High‐Molecular‐Weight Glycoprotein Released From Preimplantation Ovine and Porcine Conceptuses

Mk, Murray; Ec, Segerson; Pj, Hansen; Fw, Bazer; Roberts, R. M.

doi:10.1111/j.1600-0897.1987.tb00115.x

Cited by 39 publications

(3 citation statements)

References 41 publications

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“…Proteinaceous products from extraembryonic membranes have been reported to have thyrotropic (Avivi et al, 1982), luteotropic (Ailenberg and Shemesh, 1983), antiprostanoid (Shemesh et al, 1984;Knickerbocker et al, 1986), lactogenic (Bolander and Fellows, 1976;Beckers et al, 1980;Eakle et al, 1982;Murthy et al, 1982), and immunosuppressive (Murray et al, 1987) activities. Clearly, conceptus proteins may function as important hormones in the establishment, maintenance, and regulation of pregnancy.…”

Section: Ntr Od Uct I0 Nmentioning

confidence: 96%

Characterization of Protein Production by Bovine Chorionic and Allantoic Membranes1

Godkin

Lifsey

Baumbach

1988

Biology of Reproduction

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Bovine allantoic (A) and chorionic (C) membranes from Days 29, 32, 36, and 40 of pregnancy were isolated by dissection and cultured in a modified minimum essential medium in the presence of L-[35S]methionine to characterize in vitro synthesis and release of proteins. Membranes were also cultured in the presence of the glycosylation inhibitor tunicamycin. Proteins synthesized and released into the medium were analyzed by two-dimensional polyacrylamide gel electrophoresis and fluorography of dried gels. Stained gels were used to analyze protein from allantoic fluids. Percent incorporation of the radiolabeled amino acid into nondialyzable protein was higher for A than for C (A = 8.0 +/- 1.2 vs. C = 6.4 +/- 0.5 per 200 mg tissue) but not significantly different. C released significantly more total protein (nonradioactive) into the medium (57.0 +/- 3 vs. 9.6 +/- 0.6 micrograms/ml). Of the 25 proteins analyzed, 19 appeared to be produced primarily by one membrane or the other. In general, C was the source of a number of basic-to-neutral glycosylated proteins and A was the source of a number of more acidic glycosylated proteins. Many but not all proteins synthesized by A were present in allantoic fluid. The present study is the first to characterize protein production by isolated chorionic and allantoic membranes and to demonstrate that both tissues contribute to the production of secretory conceptus proteins.

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Section: Ntr Od Uct I0 Nmentioning

confidence: 96%

Characterization of Protein Production by Bovine Chorionic and Allantoic Membranes1

Godkin

Lifsey

Baumbach

1988

Biology of Reproduction

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“…Investigations have not yet defined the mechanism(s) responsible for the immunological survival of the ovine conceptus. It is apparent that the progesterone (P4)-treated, ovariectomized ewes have been shown to suppress in vitro T-lymphocyte proliferation in mitogen-treated, interleukin-2 (IL-2)-treated, and mixed-lymphocyte cultures (Segerson, 1981(Segerson, , 1988Staples et al, 1983;Hansen et al, 1986Hansen et al, , 1987Murray et al, 1987;Newton et al, 1989;Niwano et al, 1989;Stephenson et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Secretion of ovine lymphocyte suppressor factor from curetted uterine luminal cells

Segerson

Gunsett²

1992

Journal of Animal Science

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The secretion of ovine lymphocyte suppressor factor from jugular vein (JV), uterine vein (UV), and curetted hemopoietic uterine luminal (UL) mononuclear cells was evaluated on d 14 of the cycle, following ovariectomy (OVX) and after 14 d of progesterone injections (OVX + P4, 1 mg/kg BW). Mononuclear cells (predominantly lymphocytes) were harvested by Ficoll-Paque and placed into culture (2.5 x 10(6).mL-1.well-1 in RPMI-1640). Cellular supernatants were obtained at 72 h and volumes (5 to 50 microL) were tested for suppression of phytohemagglutinin (PHA [.08 microgram l)-treated peripheral blood lymphocytes (1.0 x 10(5)). In a concurrent experiment, PHA-treated JV, UV, and UL cells (1.0 x 10(5)) were cultured singly and JV cells (1.0 x 10(5)) were also cocultured with each of 1.0 x 10(5), 5.0 x 10(4), and 2.5 x 10(4) UV and UL cells. The incorporation of thymidine into DNA was quantified at 60 h. For the cellular supernatant experiment, thymidine incorporation was affected by reproductive phase (P less than .036), lymphocyte source (P less than .0001), and phase x source (P less than .004). For UL cells, the degree of suppressor activity follows: d 14 greater than OVX greater than OVX+P4 (P less than .05). The UL supernatant from OVX+P4-treated ewes and supernatants of JV and UV cells, irrespective of reproductive phase, lacked suppressor activity. Sephacryl S-200 chromatography revealed that UL supernatant from d-14 ewes contained a greater than or equal to 248,000 molecular weight suppressor macromolecule. For the cellular coculture experiment, thymidine incorporation was affected by reproductive phase (P less than .05) and lymphocyte source (P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Roth et al (1991) have shown that this suppressor factor, horse conceptus-derived immunosuppressive factor (HCS) has M, > 100 000. High Mr components of cultures of conceptuses and of gravid uterine fluid of other domestic species, such as cows (Segerson & Bazer, 1989), sheep Murray et al, 1987) and pigs (Murray et al, 1987), also suppress lymphocytes when used to supplement blastogenesis cultures in vitro. These suppressive factors may play a role in protecting the conceptus from maternal immunological attack during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Involvement of interleukin 2 receptors in conceptus-derived suppression of T and B cell proliferation in horses

Roth¹,

White²,

Thompson³

et al. 1992

Reproduction

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Summary. The mechanism by which a horse conceptus-derived immunosuppressive factor (HCS) of Mr > 100 000 inhibits lymphocyte proliferation was investigated. The factor was obtained from the culture supernatants of 20-day-old horse conceptuses; activity, identified by reduced uptake of [3H]thymidine by mitogen-stimulated lymphocytes, was greatest (P < 0\m=.\01) in cultures stimulated by mitogen from pokeweed. HCS also suppressed cell proliferation stimulated by phytohaemagglutinin (P < 0\m=.\01), but had no effect on lipopolysaccharide-stimulated cells (P > 0\m=.\05). Data from a fluorescence\x=req-\ activated cell sorter indicated that supplementation with HCS reduced the number of T cells in phytohaemagglutinin-stimulated cultures and suppressed proliferation of T and B cells in pokeweed-mitogen-stimulated cultures compared with controls. Cell proliferation was greater (P < 0\m=.\01) in cultures supplemented with HCS 24 h after stimulation than in those treated at the start of stimulation, and was even greater (P < 0\m=.\01) when cells were treated 48 h after stimulation. The removal of HCS from treated lymphocyte cultures resulted in complete recovery of cell responsiveness, and stimulated proliferation of treated cells did not differ (P > 0\m=.\05) from that of control cells. The addition of stimulated equine lymphocyte supernatant to cultures supplemented with HCS did not significantly increase (P > 0\m=.\05) cell proliferation in response to pokeweed mitogen.Addition of recombinant human interleukin 2 (rIL-2) to HCS-treated cultures did not alter the suppressive activity of HCS, although cell proliferation was greater in cultures supplemented with rIL-2 than in controls (P < 0\m=.\01). HCS inhibition of IL-2 receptor (IL-2R) function was investigated using an IL-2-dependent murine cytolytic T lymphocyte cell line; the fraction of HCS of Mr > 100 000 had no effect (P > 0\m=.\05) on proliferation of IL-2-dependent murine cytolytic T lymphocyte cells induced by rIL-2. Together, these data suggest that HCS suppresses proliferation of T lymphocytes during the early stages of cell activation by inhibiting IL-2R interaction and that this suppression interferes with interactions between T cells and B cells, thereby also indirectly inhibiting proliferation of B cells. The potent immunosuppressive capacity of HCS may be one factor responsible for inhibiting cell-mediated fetal allograft rejection during pregnancy.

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Suppression of Lymphocyte Activation by a High‐Molecular‐Weight Glycoprotein Released From Preimplantation Ovine and Porcine Conceptuses

Cited by 39 publications

References 41 publications

Characterization of Protein Production by Bovine Chorionic and Allantoic Membranes1

Characterization of Protein Production by Bovine Chorionic and Allantoic Membranes1

Secretion of ovine lymphocyte suppressor factor from curetted uterine luminal cells

Involvement of interleukin 2 receptors in conceptus-derived suppression of T and B cell proliferation in horses

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