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J M Decker

Publications and source records attributed to J M Decker.

At least 37 records · Page 2Linked to original sources
PubMed1984

Purification and characterization of a mannose-containing disaccharide obtained from human pregnancy urine. A new immunoregulatory saccharide.

Endogenous mammalian lectin-like sugar-binding molecules have been previously described that have immunoregulatory properties. Further, the addition of defined simple saccharides to lymphocyte cultures has been shown to inhibit a variety of in vitro lymphocyte functions, presumably because these sugars are able to compete with the binding of endogenous lectins to critical membrane receptors. In this report, we describe the isolation and characterization of a D-mannose-containing disaccharide in human pregnancy urine that inhibits the proliferative response of human T lymphocytes. The inhibitory disaccharide was purified to homogeneity by sequential steps including affinity chromatography on immobilized concanavalin A and molecular sizing on Sephadex G-75 and then Fractogel 40S columns, with final purification on high-performance thin-layer chromatography. By mass spectrometry of the purified material as its permethylated derivative, the deduced structure of this compound was alpha-D-Manp 1-6-D-Man. To confirm that this disaccharide was in fact immunosuppressive, an identical disaccharide was prepared by sequential digestion of yeast cell wall polysaccharide. The urinary and yeast disaccharides had identical immunosuppressive properties. It has been previously reported that D-mannose is inhibitory for antigen-specific proliferative assays in the range of 10-50 mM. The purified alpha-D-Manp 1-6-D-Man disaccharide was inhibitory at 100-fold-lower concentrations. Further, while D-mannose inhibits T cell proliferation when added at anytime up to 24 h before harvest of a 6-d lymphocyte culture, alpha-D-Manp 1-6-D-Man disaccharide was inhibitory only if added at the initiation of culture and had no inhibitory effect if added just 24 h later. These data support the concept that simple sugar compounds can exhibit marked immunoregulatory activity in vitro. The impact of these molecules on the regulation of immune responses in vivo is unknown, as is their precise mechanism of action, but structural and chemical identification should now permit a detailed analysis of these issues.

Chromatography, Affinity↗
PubMed1984

Inhibition of human NK cell cytotoxicity against K562 cells with glycopeptides from K562 plasma membranes.

Human Natural Killer (NK) cell activity against K562 target cells has previously been shown to be inhibited by certain monosaccharides and glycoproteins in a specific fashion. Glycopeptides have been prepared from the isolated plasma membranes of cultured K562 cells by extensive pronase digestion and fractionated by lectin affinity chromatography. Nine different fractions were tested for their ability to block 51Cr release by K562 targets in the presence of NK cells; two of the fractions, one isolated on RCA I lectin and the second on Pea lectin, were very effective at blocking cytotoxicity (greater than 80% inhibition) while the other fractions were only marginally effective. Furthermore, evidence is presented which demonstrates the blocking activity of the glycopeptides occurred at a lytic rather than a recognition step.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

Induction of cytotoxic effector activity in the HL-60 promyelocytic cell line by incubation with phorbol myristate acetate: a model system of human spontaneous monocyte-mediated cytotoxicity.

In an attempt to develop a constant and reproducible in vitro system for a detailed analysis of cytotoxic effector mechanisms of nonimmune mononuclear phagocytes, the HL-60 promyelocytic cell line was studied for its cytotoxic action on chicken erythrocyte target cells. HL-60 cells cultured in complete medium were found to be noncytotoxic for chicken erythrocytes in an 18-hr 51Cr-release assay. These cells have been shown to acquire several characteristics of mature macrophages upon incubation with phorbol myristate acetate (PMA), and when PMA was included in the medium during the assay, the HL-60 cells became strongly cytotoxic to the target cells in the absence of exogenous antibody, lectin, or serum complement. Freshly isolated peripheral blood monocytes also became cytotoxic in the presence of PMA, whereas peripheral blood lymphocytes and the U937 histiocytic cell line did not. Detectable target lysis was observed between 4 and 8 hr after HL-60 stimulation with PMA, and HL-60 cells prestimulated with PMA for 24 hr retained their cytotoxic activity following washing and assay in PMA-free medium. Cytotoxic HL-60 cells developed after exposure to 10(-6) to 10(-9) M PMA, and significant target cell lysis occurred at effector:target cell ratios as low as 0.5:1. The PMA-induced HL-60-mediated cytotoxic response was markedly inhibited by blockers of protein synthesis, inhibition of microfilament function, and depletion of cellular superoxide and hydrogen peroxide. Interestingly, cytotoxicity of HL-60 cells for chicken erythrocyte targets was modulated by the direct addition of certain simple saccharides to the assay in a fashion similar to that observed with spontaneously cytotoxic mononuclear cells from several vertebrate and invertebrate species. Thus, the cytolytic effector function induced in HL-60 cells by incubation with PMA presents a useful model for the study of cellular cytotoxic mechanisms as well as the mechanisms utilized by nonimmune cells in the recognition of non-self.

Animals↗
PubMed1983

Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies.

Antibodies which react with products encoded by the human DR locus precipitate a biomolecular membrane glycoprotein complex with m.w. of 29,000 and 34,000 daltons. Such antibodies are directed against HLA-DR Ia-like antigens found on human B cells and human monocytes and have been shown previously to inhibit a variety of in vitro cellular and humoral immune reactions. We have compared the in vitro effects of such antibodies on two assays of human immunity: antigen-specific proliferation and polyclonal immunoglobulin production. Intact IgG fractions of a rabbit heteroantiserum (anti-P29,34), a human MT-2 locus alloantiserum (Ia 172), and a mouse monoclonal antibody (LB 3.1) markedly inhibited in vitro immune reactivities of human mononuclear cells. Interestingly, F(ab')2 preparations of these antibodies failed to inhibit these in vitro immune responses at the concentrations tested. These data suggest that under certain conditions, Fc domains play a critical role in the inhibitory activity of antibodies to Ia-like molecules.

Animals↗
PubMed1982

Cooperative interaction of factor B and other complement components with mononuclear cells in the antibody-independent lysis of xenogeneic erythrocytes.

Synergistic cytotoxicity is a term used to describe a cytotoxic system in which xenogeneic erythrocyte target cells are lysed in the presence of nonimmune human mononuclear effector cells and antibody-depleted normal human serum. Neither the mononuclear cells nor the serum alone are cytolytic to the target erythrocytes. Previous studies have shown that the serum activity is not immunoglobulin and is heat-labile, suggesting a similarity to serum complement. In this report, sera deficient in various complement components as well as highly purified single complement components were tested with whole mononuclear cell populations and purified monocytes and lymphocytes to further characterize this cytotoxicity system. Whole mononuclear cell populations failed to mediate target cell lysis in sera deficient in C5 or factor B. However, C3-deficient serum, even in the presence of anti-C3 antibody, supported synergistic cytotoxicity normally. Purified lymphocytes were also normally cytotoxic in C3-deficient serum but failed to lyse targets in sera deficient in C5, C7, C8, or depleted of factor B. Purified monocytes failed to lyse the target cells only in factor B-depleted serum and could lyse the target cells in serum-free medium when purified factor B alone was added. Monocyte-mediated cytotoxicity induced by factor B was inhibited 73-100% by adding lymphocytes back to the purified monocytes. Thus, both lymphocytes and monocytes can serve as effector cells in this form of cytotoxicity but require cooperative interaction with different sets of complement components. In addition, lymphocytes can modulate the monocyte-mediated form of target cell lysis associated with factor B.

Animals↗
PubMed1982

Evidence that antisera that react with products of the human HLA-DR locus may block in vitro antigen-induced proliferation by inducing suppression.

It is widely recognized that antisera that interact with determinants encoded by the Ia region of the mouse and its counterpart, the DR locus of man, are capable of interfering with the ability of monocytes and lymphocytes to respond in vitro to an antigenic stimulus. Using an in vitro assay that measures antigen-specific proliferation of human lymphocytes, we found that both a heteroantiserum raised in rabbits (anti-P29,34) and alloantisera which recognize determinants encoded for by the human DR locus dramatically block in vitro antigen-specific proliferation. These anti-DR antisera appear to act at the level of the monocyte; monocytes pulsed and washed free of excess antisera fail to promote proliferation in the presence of soluble antigen and untreated T cells whereas identically pulsed and washed T cells respond normally with untreated monocytes. Furthermore, the addition of unpulsed monocytes fails to restore in vitro antigen-specific reactivity. Our data suggest that membrane-bound anti-DR-specific antisera on monocytes is profoundly suppressive, and also suggests simple steric hindrance may not account for all of the observed effects such antisera have on monocyte-T cell interactions.

Antibody Affinity↗
PubMed1981

Effector cell sensitivity to sugar moieties. I. Inhibition of human natural killer cell activity by monosaccharides.

Human natural killer (NK) cells recognize multiple target antigens. The ligands (antigens) involved in the effector-target cell interaction have not been extensively identified. In the present study, assays of NK activity in the presence of a panel of monosaccharides demonstrated inhibition of cytolysis in a dose-response fashion. We propose that NK cell activity involves the recognition of carbohydrate structures on target cells via receptors on the effector cell surface.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Spontaneous cytotoxicity by human peripheral blood monocytes: inhibition by monosaccharides and oligosaccharides.

The mechanism by which nonimmune cytotoxic effector cells recognize "foreign" targets for cytotoxic attack was investigated utilizing a model system in which cultured human monocytes become cytotoxic to a broad variety of xenogeneic erythrocyte target cells. Such spontaneously cytotoxic human monocytes lyse targets such as chicken (CRBC), horse (HRBC), and rat (RRBC) erythrocytes rapidly and without the addition of exogeneous lectin or antibody. It was found that a variety of simple sugars were capable of blocking the expression of cytotoxicity by precultured human monocytes, and that different oligosaccharides blocked the killing of different targets. For example, cellobiose, a beta 1-4 dimer of D (+) glucose, blocked, CRBC and HRBC lysis in vitro, but had no effect on RRBC lysis. Arabinogalactan (a complex polysaccharide with a galactose beta 1-3 galactose backbone and galactose beta 1-6 galactose side chains with terminal arabinoses), however, blocked HRBC killing, but exhibited only minor inhibition of CRBC killing. Other aspects of cell-mediated function, including lymphocyte transformation to PHA, cell viability as assessed by trypan blue exclusion, monocyte phagocytosis of opsonized CRBC's, and PHA-induced cellular cytotoxicity of CRBC targets, were essentially intact in the presence of identical concentrations of oligosaccharides. Such target-specific inhibition is consistent with the hypothesis that cytotoxic human monocytes recognize various targets through surface receptors which interact with specific monosacchardies, disaccharide, and oligosaccharide sequences present on the target surface.

Animals↗
PubMed1980

Defective monocyte killing in patients with malignancies and restoration of function during chemotherapy.

Spontaneous monocyte-mediated cytotoxicity (SMMC) in 34 patients treated with a chemotherapeutic regimen including cisplatin for various malignancies was depressed (median 7% 51Cr release) compared with SMMC in 31 normal controls (median 43%; p < 0.0001). Cytotoxicity in 7 patients with stage III or IV ovarian carcinoma was then followed during six cycles of chemotherapy with a cisplatin-containing regimen. All patients had initial cytotoxic values of < 8%, and in all SMMC increased at least three-fold between the third and fifth cycle of chemotherapy. This study lends support to the concept that cancer patients have depressed monocyte function. Cisplatin-containing chemotherapy seems to enhance monocyte function in vitro and in vivo.

Cisplatin↗
PubMed1980

Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes.

We have previously shown that monosaccharides and disaccharides will block the expression of spontneous monocyte-mediated cytotoxicity. Our data were consistent with the hypothesis that human mononuclear cells express lectin-like receptors that are capable of binding to a variety sugar moieties found on target cell membranes. In this communication, we will present evidence that monosaccharides and disaccharides are also capable of blocking the expression of T cell reactivity as measured by an in vitro antigen-specific proliferative assay. The majority of sugars that blocked monocyte-mediated cytotoxicity had no effect on antigen-specific proliferation. Those sugars that did suppress antigen-induced proliferation had no effect on PHA-induced proliferation. Furthermore, some of these sugars only inhibited if they were added at the initiation of the assay; they failed to inhibit if added 24 hr after the initiation of the assay. Antigen-pulsing experiments suggested that these sugars did not block antigen uptake by human monocytes. These data suggest that a variety of cellular interactions may be mediated by receptors with specificity for simple sugars. The ability to block these naturally occurring lectins specifically both in vitro and in vivo may prove to be a powerful tool for dissecting out various forms of cellular recognition and collaboration.

Acetylgalactosamine↗
PubMed1979

MICC cytotoxic effector function of human T lymphocyte subpopulations bearing Fc-receptors for IgG and IgM.

Purified subpopulations of human T lymphocytes bearing Fc-IgG and Fc-IgM receptors were studied for their ability to mediate mitogen (PHA) induced cellular cytotoxicity (MICC) to chicken erythrocyte (CRBC) and DBA/Mastocytoma P815Y tumour cell targets. There were marked differences in the ability of the Fc-IgG receptor-bearing T cell (T gamma) and the Fc-IgM (T mu) to mediating MICC to CRBC and P815Y target cells. T gamma cells were very efficient killers of CRBC and T mu cells had no cytotoxic activity to CRBC. On the other hand, both the T gamma and T mu subpopulations were able to mediate MICC to P815Y tumour cell targets.

Cytotoxicity, Immunologic↗
PubMed1979

Synergistic cytotoxicity. II. In vitro arming of monocytes and T cells by a heat labile fraction of human plasma.

In a previous paper we demonstrated that freshly obtained human plasma contain a heat labile nonantibody factor that induced human mononuclear cells to become nonspecifically cytotoxic toward xenogeneic but not allogeneic RBC targets. We now present evidence that this factor has a loose affinity for human monocytes and human T cells and can arm then to kill xenogeneic RBC targets. Furthermore, proteolytic enzymes markedly enhance this arming effect. This ability to be armed by a heat labile component found in fresh human plasma and the fact that proteolytic enzymes markedly enhance cytotoxicity clearly dissociate this model of nonspecific cytotoxicity for previously reported NK models.

Absorption↗
PubMed1979

Spontaneous cytotoxicity. III. Inhibition of human monocyte mediated cytotoxicity by pokeweed mitogen.

We have shown that human mononuclear cells become spontaneously cytotoxic to a variety of erythrocyte targets after 7 days of in vitro culture. This phenomenon of spontaneous cytotoxicity occurs in low concentration of either autologous serum of FCS and is independent of any known stimulant. It does not require exogenous antibody, mitogen, or antigen. Once expressed, the cytotoxic cell has little, if any, specificity. Monocytes appear to be responsible for this observed in vitro cytotoxicity. We now present evidence that the development of spontaneous monocyte-mediated cytotoxicity in vitro is completely reversed by the addition of optimally mitogenic doses of PWM. PWM appears to reverse monocyte-mediated killing by stimulating a potent cell-mediated suppressor. This suppressor cell is radiosensitive and its action is blocked by inhibitors of protein synthesis. In contrast to other mitogen-driven suppressor models, PWM will inhibit spontaneous monocyte-mediated cytotoxicity even when added as late as 6 hr before the end of a 7-day culture.

Cell Separation↗
PubMed1979

Synergistic cytotoxicity. I. Characterization of a heat labile plasma fraction that induces nonspecific cytotoxicity by human mononuclear cells.

The mechanism by which non-immune mononuclear cells recognize invading foreign material and are activated for cytotoxic attack was studied in a model system employing human mononuclear cells, fresh plasma, and 51Cr-labeled xenogeneic target erythrocytes. In these experiments, fresh antibody-depleted plasma or mononuclear leukocytes alone were poorly cytotoxic to xenogenic erythrocytes. However, these target cells were rapidly lysed when both fresh antibody-depleted plasma and mononuclear cells were present in the assay. The plasma factor could not be removed by extensive absorption with the target cells, was present in plasma from hypogammaglobulinemic patients, was heat labile, and was sensitive to incubation with zymosan and cobra venom factor. The "antigen" specificity of this reaction was directed by the serum factor inasmuch as target cells autologous to the effector cells could be killed in the presence of antibody-depleted xenogeneic plasma, but not autologous plasma. These data suggest that an important mechanism for the recognition of "foreigness" by non-immune mononuclear cells is via interaction with a plasma component, possibly a factor related to serum complement.

Absorption↗