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Biomedical subjects

L Shen

Publications and source records attributed to L Shen.

At least 307 records · Page 17Linked to original sources
PubMed1986

Glucocorticoid enhances gamma interferon effects on human monocyte antigen expression and ADCC.

The expression of HLA-DR antigen by highly enriched human monocytes cultured in serum free medium was found to be markedly elevated by human recombinant gamma interferon (IFN-gamma). This effect was maximal after 48 h in culture with 300 mu/ml IFN-gamma. Class I MHC antigen also increased with IFN-gamma treatment. By contrast, binding of a myeloid-specific monoclonal antibody, AML-2-23, was dramatically decreased by IFN-gamma. The augmentation of MHC antigens was not ablated by an immunosuppressive concentration (2 X 10(-7) M) of the glucocorticoid dexamethasone (DEX). In fact, both the enhancement of Class I and Class II MHC antigen expression and the suppression of AML-2-23 antigen by IFN-gamma were often more profound in the presence of DEX. IFN-gamma treatment also resulted in elevated monocyte effector function, as measured by antibody dependent cellular cytotoxicity (ADCC). This functional activation was not inhibited by DEX. On the contrary, DEX slightly augmented IFN-gamma effects on ADCC. This contrasts with other reports that glucocorticoids inhibit monocyte responsiveness to lymphokines, and suggests that the interplay between lymphokines and the glucocorticoid hormones may be more complex than previously thought.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Nuclear magnetic resonance studies of carbohydrate metabolism and substrate cycling in Fasciola hepatica.

We have been interested in clarifying unique features of glycolytic metabolism in parasitic trematodes and in developing improved methods for monitoring the effects of pharmacologic agents that may alter functions of the pathway. In the present study metabolism of [1-13C]glucose by the common liver fluke, Fasciola hepatica, was studied both directly with 13C NMR and indirectly by observation of 13C-induced multiplet splitting of the 1H NMR resonances from the glycolytic end-products propionate and acetate. The extent of 13C enrichment of the end-products demonstrated that exogenous glucose was the predominant source of glycolytic substrate under the incubation conditions used. Specific enrichments of propionate and acetate in 13C were similar and enrichments at the acetate C-1 carboxyl and C-2 methyl were identical, demonstrating that acetate is generated preferentially from pyruvate formed by the malic enzyme reaction. End-product synthesized in substrate-free medium following incorporation of a small fraction of [1-13C]glucose into endogenous glycogen demonstrates that glucose equivalents from the most recently synthesized polymeric chains, which have a specific activity in 13C equal to that of the exogenous glucose, are preferentially used for glycogenolysis. Stimulation of flukes with 0.1 mM serotonin results in a reduction of the propionate/acetate 13C enrichment ratio consistent with functional "compartmentation" of glycogen pools having different structures and/or specific enrichment in 13C. Glucose equivalents were incorporated into glycogen in intact flukes with label at both the C-1 and C-6 positions during perfusion with [1-13C]glucose as a consequence of "substrate cycling" at the phosphofructokinase/fructosebisphosphatase enzyme couple. The observed glycogen C-6/C-1 labeling ratio of 0.42 and the net glycolytic flux of 11 mumol/g wet weight/hr imply a total forward flux of about 29 mumol/g wet weight/hr through phosphofructokinase with a reverse flux of about 17 mumol/g wet weight/hr through fructosebisphosphatase. Net glycolytic flux is therefore a poor estimate of the true flux through phosphofructokinase in this preparation.

Acetates↗
PubMed1985

1,25-Dihydroxyvitamin D3 induces a myelomonocytic phenotype with enhanced effector cell function in the HL-60 promyelocytic leukemia cell line.

Human promyelocytic leukemia (HL-60) cells were induced by 1,25-dihydroxyvitamin D3 (calcitriol) to differentiate and examined using a panel of monoclonal antibodies (MoAbs) and functional assays. Although morphologically and histochemically these cells appeared to be of the monocyte-macrophage phenotype, there was a decline in Fc receptors for IgGl and no induction of class II HLA antigens. There was, however, dramatic induction of the antigen detected by the myeloid-specific MoAb AML-2-23. These data suggest that the phenotypic changes induced by calcitriol in HL-60 cells are consistent with myelomonocytic differentiation in that the resultant cells possess characteristics of both monocytes (morphology, non-specific esterase staining, high levels of AML-2-23 reactivity) and granulocytes (PMN 29 binding, decreased Fc receptors for IgGl, absence of class II HLA antigens). Perhaps more important, the ability of calcitriol-treated cells to perform antibody-dependent cellular cytotoxicity and phagocytosis was markedly augmented. Lysis of antibody-coated erythrocytes by HL-60 cells increased from 5% in controls to 30-35% with calcitriol treatment for 4 days. This enhanced effector cell function was seen despite a decline in Fc receptors measured by cytofluorography. These data suggest that calcitriol may be involved in both differential and functional activation of myeloid cells.

Antibodies, Monoclonal↗
PubMed1985

The expression of receptors for IgA on human monocytes and calcitriol-treated HL-60 cells.

In this study, we investigated the expression of IgA Fc receptors (FcR alpha) by human myeloid cells. By using a sensitive cytofluorometric IgA binding assay, we found that approximately 85% of peripheral blood monocytes bound IgA in an isotype-specific fashion. The HL-60 human promyelocytic leukemia cell line failed to express FcR alpha; however, treatment of HL-60 cells with the differentiating agent calcitriol induced the expression of FcR alpha on greater than 90% of these cells. Monocytes and calcitriol-treated HL-60 cells were capable of ingesting IgA-coated erythrocyte targets, suggesting that phagocytosis could be mediated through FcR alpha. The induced HL-60 cell system represents a useful model for further studies on FcR alpha expression and function.

Antigens, CD↗
PubMed1984

Immunological monitoring in patients with end-stage renal disease.

Parameters of cell-mediated immune function were determined in 76 patients with end-stage renal disease. Lymphocyte subpopulations (OKT3, OKT4, OKT8, OKIa1, OKM1, OKT9, OKT10), natural killer (NK)-cell activity (percentage 51Cr release from K562 targets), and delayed cutaneous hypersensitivity were measured and correlated with other variables. The results indicate that (1) uremic patients have a significant diminution in the OKT4-lymphocyte subpopulation and OKT4/OKT8 (helper/suppressor) ratio compared to normal controls; (2 blood transfusions do not induce significant alterations in the helper/suppressor-cell ratio; (3) uremic patients have a significant increase in OKM1 cells compared to normal controls; (4) the majority of uremic patients in this series developed delayed cutaneous hypersensitivity responses to recall antigens and could be de novo sensitized to 2,4-dinitrochlorobenzene (DNCB); (5) skin-test reactivity could not be correlated with total circulating T cells or levels of any lymphocyte subpopulations; and (6) NK-cell activity in uremic patients is not significantly different from that in normal controls. These results highlight the varying levels and function of different lymphocyte subsets in patients with end-stage renal disease when they are treated with chronic maintenance hemodialysis.

Adult↗
PubMed1984

Direct stimulation of ADCC by cloned gamma interferon is not ablated by glucocorticoids: studies using a human monocyte-like cell line (U-937).

We have used the macrophage-like cell line U-937 to demonstrate that recombinant gamma (immune) interferon (gamma-IFN) acts directly on the mononuclear phagocyte in the absence of other cell types to increase Fc receptor sites and antibody-dependent cellular cytotoxicity (ADCC). Incubation of U-937 for 18 hr with 2% gamma-IFN-rich supernatant, or with 10 U/ml of pure recombinant gamma-IFN, resulted in a seven-fold increase in Fc receptors as measured by the binding of radiolabeled IgG or fluoresceinated IgG and cytofluorography. Simultaneous measurement of ADCC for chick erythrocytes showed a seven-fold increase. This augmentation of Fc receptors and function was not ablated by an immunosuppressive cocn of the glucocorticoid dexamethasone. The potent effects of gamma-IFN both on surface receptors and effector functions of macrophages suggest that it is an important mediator in the efferent limb of immunity. Moreover, our findings that physiologic levels of glucocorticoids do not block activation of the mononuclear phagocyte support our view that glucocorticoids are immunosuppressive as a result of their action on gamma-IFN-producing cells. This would seem an important consideration in the development of potential strategies for obviating steroid-induced immunosuppression.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Gamma interferon induces monocytoid differentiation in the HL-60 cell line.

We investigated the ability of purified, recombinant DNA-derived interferons (IFN) to induce phenotypic changes in cells of the HL-60 promyelocytic leukemia cell line. Changes in cell surface markers detected by monoclonal antibodies as well as morphologic, histochemical, and functional changes were monitored. We found that gamma-IFN, but not alpha- or beta-IFN, induced the expression of antigens characteristic of monocytes and granulocytes (AML-2-23, 63D3, and 61D3), as well as changes in morphology consistent with monocytoid differentiation. These included induction of alpha-naphthyl acetate esterase, increased cell size, and a decrease in azurophilic granules. The gamma-IFN dose dependency and time course of the effect on antigen expression suggest that de novo protein synthesis was induced by gamma-IFN. The activity of gamma-IFN and of mixed-lymphocyte culture supernatant was blocked by a monoclonal antibody to gamma-IFN. Significant augmentation in the ability of the HL-60 cells to mediate antibody-dependent cellular cytotoxicity was induced by gamma-IFN. These findings suggest that gamma-IFN plays a role in the regulation of hematopoiesis.

Antibodies, Monoclonal↗
PubMed1984

Differentiation of a human monocytic cell line by 1,25-dihydroxyvitamin D3 (calcitriol): a morphologic, phenotypic, and functional analysis.

Several recent studies have suggested a role for 1,25-dihydroxyvitamin D3 (calcitriol) in myeloid differentiation. We have examined the effects of calcitriol on the U937 monoblast cell line and found that calcitriol, at near physiologic concentrations, is a potent inhibitor of U937 growth. Moreover, calcitriol induces differentiation to a monocyte-macrophage phenotype marked by enhanced alpha-naphthyl esterase staining. Morphologic changes were attended by de novo induction of the myeloid specific antigen detected by the monoclonal antibody AML-2-23, as well as dramatic increases in Fc receptors for IgG. In addition, calcitriol induced U937 cells to perform phagocytosis and antibody-dependent cellular cytotoxicity. These results indicate the potential activity of calcitriol in myeloid differentiation and additionally suggest a role for calcitriol in monocyte-macrophage activation.

Antibodies, Monoclonal↗
PubMed1983

Cytofluorographic analysis of receptors for IgA on human polymorphonuclear cells and monocytes and the correlation of receptor expression with phagocytosis.

Receptors for the Fc portion of IgA (RFc alpha) were identified on human monocytes and polymorphonuclear cells (PMNs) by cytofluorograph analysis using FITC-labeled IgA and by rosette formation with IgA-sensitized indicator cells. Larger percentages of PMNs obtained from the oral cavity expressed RFc alpha than did blood PMNs. These oral PMNs also expressed more RFc alpha per cell than blood PMNs. Moreover, the expression of these receptors on blood PMNs was enhanced by overnight incubation with IgA. In functional studies, RFc alpha appeared to cooperate with receptors for IgG in enhancing blood and oral PMN mediated phagocytosis of target cells coated with IgG and IgA. Furthermore, and in contrast with blood PMNs, oral PMNs were capable of phagocytosing target cells coated with IgA alone. Thus, receptors for IgA may be important to the ability of RFc alpha bearing effector cell populations to mediate protection at mucosal surfaces.

Cells, Cultured↗
PubMed1983

Contribution of fibrin stabilization to clot strength. Supplementation of factor XIII-deficient plasma with the purified zymogen.

The contribution of fibrin stabilization to clot strength, measured as the static elastic modulus, was evaluated in human plasma by two independent procedures. In the first approach, amine inhibitors of fibrin stabilization were examined for their effects on the rigidity of normal plasma clots. It is a unique property of these inhibitors that they do not interfere with the reversible aggregation of fibrin molecules, i.e., do not delay clotting time, but selectively prevent only the formation of gamma-glutamyl-epsilon-lysine protein-to-protein linkages. Though the compounds tested were of different chemical structures and potencies, a fivefold reduction in clot strength was obtained in each instance. This value of 20% of normal seems to correspond to the rigidity of the Factor XIII-deficient plasma clot because, as demonstrated by the second approach, when a plasma specimen that genetically lacked the fibrin stabilizing factor was supplemented by the addition of measured amounts of the purified zymogen, a fivefold increase in clot strength could be achieved. The described procedure of evaluating Factor XIII in terms of correcting the elastic modulus of a deficient plasma clot is considered an important assay for the functional competence of purified preparations of the zymogen for the purpose of therapeutic application.

Aminoacetonitrile↗
PubMed1982

Monoclonal antibodies to novel myeloid antigens reveal human neutrophil heterogeneity.

Three cytotoxic murine monoclonal antibodies that recognize myeloid-specific antigens have been produced by immunization with normal human neutrophils or myeloblasts from a patient with acute myelomonocytic leukemia. Two of these, PMN 6 and PMN 29, are specific for neutrophils; the third monoclonal antibody, AML-2-23, is reactive with the majority of normal monocytes as well as a subpopulation of mature neutrophils. Although neutrophils from all individuals tested expressed these antigens, cytofluorographic analysis revealed that the percentage of cells bearing the PMN 6 and AML-2-23 antigens varied among individuals. Significant additional heterogeneity in the density of each antigen among antigen-bearing cells was also observed. All three antibodies efficiently mediated complement-dependent cytotoxicity of acute myelocytic leukemia cells yet were unreactive with lymphocytic leukemia cells. Neutrophil cytotoxicity was mediated by PMN 6 and PMN 29 but not by AML-2-23. On the other hand, AML-2-23, but not PMN 6 or PMN 29, was cytotoxic for normal monocytes and macrophages. These monoclonal antibodies may be of value in the study of normal neutrophil function and differentiation and may have clinical utility in diagnosis and therapy of myeloid leukemia.

Animals↗
PubMed1982

Studies on autoantibodies to poly (adenosine diphosphate-ribose) in SLE and other autoimmune diseases.

Sera from 41 patients with systemic lupus erythematosus (SLE), 87 controls with various diseases, and 30 normal subjects were examined for poly (adenosine diphosphate-ribose) and ds DNA binding. Elevated levels of poly (ADP-ribose) binding were found in 73% of the SLE patients compared with 58% who had raised ds DNA binding. In a further study of 160 sera from 27 patients with SLE, levels of antipoly (ADP-ribose) antibodies were shown to correlate with clinical activity better than either anti-ds DNA or ss DNA antibodies.

Adult↗
PubMed1981

Inhibition of lymphocyte capping and transformation by propranolol and related compounds.

1 The effects of propranolol on phytohaemagglutinin (PHA)-induced transformation of murine T lymphocytes and capping of anti-IgG on the surface of murine B lymphocytes have been examined. 2 A 50% inhibition of transformation was observed with 10(-5) M propranolol, whereas a higher concentration, of the order of 10(-3) M propranolol was required to inhibit capping by 50%. The (+)-and (-)-isomers of propranolol proved equipotent in these respects, and the relative potencies of selected analogues of propranolol (alprenolol, oxprenolol, metoprolol, practolol, and sotalol) coincided with their potencies as membrane stabilizers; however, lymphocyte transformation was consistently more sensitive than capping. 3 Similar effects were also seen with quinidine, chlorpromazine and lignocaine, and it was concluded that the inhibition of both lymphocyte functions was due to the membrane stabilizing actions of propranolol.

Adrenergic beta-Antagonists↗