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Biomedical subjects

A A Wadee

Publications and source records attributed to A A Wadee.

At least 55 records · Page 3Linked to original sources
PubMed1987

Gamma interferon reverses inhibition of leukocyte bactericidal activity by a 25-kilodalton fraction from Mycobacterium tuberculosis.

In this study we examined the effects of Mycobacterium tuberculosis cell extracts on the phagocytic activity of polymorphonuclear leukocytes and cultured peripheral blood monocytes. M. tuberculosis cell extracts were fractionated on Sephacryl S-200 columns, and a 25-kilodalton glycolipoprotein was shown to inhibit the intracellular killing ability of these leukocytes but had no effect on their phagocytic potential. This same fraction inhibited fusion of phagosomes with lysosomes, as assessed by noting the transfer of acridine orange from lysosomes to phagosomes. This fraction was shown to have a maximal inhibitory effect when it was in the form of an intact carbohydrate-lipid-protein complex. Gamma interferon (IFN-gamma), but not IFN-alpha, reversed the inhibitory effect of the mycobacterial component on bactericidal activity and on fusion of phagosomes and lysosomes. Thus, this 25-kilodalton fraction of M. tuberculosis cell extract may be important in protecting organisms against phagocytic degradation, an effect which can be reversed by IFN-gamma.

Bacterial Proteins↗
PubMed1987

Characterization of immunosuppressive proteins of Brugia malayi microfilariae.

Inhibition of Concanavalin A-induced lymphocyte proliferation was used to monitor the partial purification and characterization of suppressor molecules from microfilariae of Brugia malayi. Suppressor activity was present in high molecular weight fractions of microfilarial extracts (Mr greater than 50 kd on SDS-PAGE) and was protease-sensitive but resisted treatment with sodium periodate, indicating that it is associated with parasite proteins. Suppressor activity was released by microfilariae cultured in vitro and could be detected in peritoneal exudates of intraperitoneally-infected jirds and in lymph and sera from athymic C3H/HeN mice with patent B. malayi infections. These findings indicate that immune unresponsiveness during patent filarial infections may result from the in vivo release by microfilariae of high molecular weight proteins that suppress host immune responses.

Animals↗
PubMed1986

Microfilariae of Brugia malayi contain a T cell mitogen.

We investigated the mechanisms that lead to polyclonal hypergammaglobulinemia in persons exposed to or infected with lymph-dwelling filarial parasites. Extracts of microfilariae of Brugia malayi induce the in vitro proliferation of lymphocytes from nonsensitized donors. The mitogenic factor(s) responsible for this effect is of low molecular weight (Mr) and acts on T4+ cells but not on T8+ T lymphocytes or on B cells. T4+ lymphocytes stimulated with filarial mitogen augment the in vitro production of immunoglobulins by autologous B lymphocytes.

Animals↗
PubMed1986

Aberrant expression of HLA-DR antigen on valvular fibroblasts from patients with active rheumatic carditis.

Immunofluorescence and immunoperoxidase staining was used to investigate the expression of Class II major histocompatibility antigens in myocardial tissue of 16 patients with acute rheumatic carditis. Aberrant expression of HLA-DR was examined using monoclonal anti-Ia antibodies and was detected on the valvular fibroblasts of those valves with ongoing active carditis. Sections of myocardial and valvular tissue from normal controls or from patients dying of other cardiac diseases did not express HLA-DR. The aberrant expression of HLA-DR on valvular fibroblasts could be important in triggering autoimmune destruction in that these cells could present self-antigens to sensitized T-lymphocytes which could initiate autoantibody production or direct destruction of local tissue.

Acute Disease↗
PubMed1985

Defective monocyte function in patients with systemic lupus erythematosus.

Peripheral blood adherent cells from patients with systemic lupus erythematosus (SLE) were shown to have markedly reduced phagocytic activity as compared to normal adherent cells or those from non-SLE patients receiving corticosteroid therapy. Both resting and phagocytosing monocytes showed decreased hexose monophosphate shunt and glycolytic activity. Mononuclear cells from SLE patients showed grossly impaired proliferative activity after NaIO4 activation. Furthermore, addition of SLE adherent cells to normal adherent cell-depleted lymphocytes decreased [3H]thymidine incorporation of the latter cells following NaIO4 treatment. Addition of normal adherent cells to SLE lymphocytes corrected the previous defect, indicating that an adherent abnormality is responsible for the defect in SLE mononuclear cell proliferation to NaIO4 activation.

Blood Bactericidal Activity↗
PubMed1985

Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome.

To investigate the pathogenesis of macroglobulinemia in the tropical splenomegaly syndrome (TSS), we assessed the functional activity of B lymphocytes and T cell subsets in a pokeweed mitogen-driven assay of immunoglobulin synthesis. Mononuclear cells from patients with TSS produced more IgM than cells from village or from distant controls. This appeared to result from a decrease in the number and/or activity of suppressor T cells of the T8+ phenotype. The lack of functional suppressor T lymphocytes was associated with the presence in sera from patients with TSS of IgM antibodies that specifically killed T8+, 9.3-, 60.1+ T cells from normal donors. These results support the hypothesis that macroglobulinemia in TSS results from defective immunoregulatory control of B cell function, and that this may be caused by lysis of suppressor T cells by specific lymphocytotoxic antibodies produced by patients with this syndrome.

Antibody Formation↗
PubMed1983

Mononuclear cell function in Mycobacterium tuberculosis infected guinea pigs.

In this study mononuclear cell function was studied in the lymph glands, spleen, and peripheral blood of Mycobacterium tuberculosis infected guinea pigs. Adherent cells from draining lymph nodes and spleens of infected animals spontaneously produced a factor which inhibited normal lymphocyte proliferative responses. As it has previously been shown that this factor activates a population of suppressor T cells, resident lymphocytes in the lymph nodes and spleen were examined and were shown to inhibit normal lymphocyte functions. It is suggested that adherent cells ingesting M. tuberculosis spontaneously release a suppressor cell activating factor (SCAF) which locally activates lymphocytes to become suppressor cells. Even at a time of overwhelming infection, peripheral blood adherent cells could not be shown to release SCAF and peripheral blood suppressor cells could not be identified. Although peripheral blood lymphocyte proliferative responses to PHA were normal in infected animals, their ability to produce the lymphokine macrophage inhibition factor was considerably reduced after the second week of infection. This dissociation between lymphocyte proliferation and lymphokine production is similar to that previously described in humans overwhelming tuberculosis.

Animals↗
PubMed1983

Characterization of a suppressor cell-activating factor (SCAF) released by adherent cells treated with M. tuberculosis.

Peripheral blood adherent cells ingesting killed Mycobacterium tuberculosis release a suppressor cell-activating factor (SCAF) into their culture supernatants. When adherent cells ingested 125I-labeled M. tuberculosis, radioactivity could be detected in the supernatant within 2 hr. When this supernatant was fractionated on a Sepharose 2B column, the fraction with suppressor cell-activating activity was also found to contain the majority of the radiolabel, which suggests that the macrophage processed bacteria (or bacterial product) constituted the major portion of the SCAF. This fraction also contained a high proportion of lipid, and the fraction with suppressor activity resided purely within the phospholipid fraction. By employing thin layer chromatography, the phospholipids responsible were identified as phosphatidylethanolamine and phosphatidylinositol. These results indicate that when macrophages ingest mycobacteria, they release phosphatidylethanolamine and phosphatidylinositol of bacterial origin into their culture supernatants, which are responsible for activating suppressor T cells.

Cell Adhesion↗
PubMed1983

Binding of phosphatidylethanolamine and phosphatidylinositol to OKT8+ lymphocytes activates suppressor cell activity.

The phospholipids phosphatidylethanolamine (PE) and phosphatidylinositol (PI) have been shown to activate a population of OKT8-enriched lymphocytes to become activated suppressor cells that result in the suppression of lymphocyte blastogenesis to a variety of mitogens and antigens. This suppression is dose dependent, and maximal suppressor activity is obtained at concentrations of 125 micrograms/ml PE and 25 micrograms/ml PI. Activation of the suppressor cell population is not associated with an actual increase in the number of cells expressing the OKT8 antigen, but the number of these cells expressing Dr antigens on their surface was increased. Both PE and PI bound to lymphocytes in a specific manner. Binding of radiolabeled PE could be inhibited by unlabeled PE but not by PI or phosphatidylserine (PS). Similarly, the binding of PI to lymphocytes was also found to be specific. Although radiolabeled PE bound to lymphocytes other than OKT8+ cells, and to other peripheral leukocytes, it bound to OKT8+ cells with a significantly greater affinity than it did to the other cell types. The Kd for PE was 1 x 10(2) nM and for PI was 1 x 10(3) nM, and receptor cell densities for these two phospholipids were estimated at 1 x 10(-8) nM and 3 x 10(-9) nM, respectively. The receptors for these two phospholipids were trypsin and heat sensitive, and the receptor sites could be regenerated after a 24-hr incubation after trypsinization.

Antibodies, Monoclonal↗
PubMed1981

Eosinophil degranulation. Monitoring by interference contrast microscopy.

A method is described for the quantitative monitoring of human eosinophil degranulation using interference contrast microscopy. Using staphyloccoci as a stimulus, degranulated cells appeared larger than nondegranulating cells, were ameboid in shape and exhibited large nude areas of cytoplasm with prominent nuclei. Granules were observed to marginate along the plasma membrane and discharge into the exterior of the cell. Eosinophils that were not induced to degranulate were spherical in shape and the cytoplasm contained numerous granules that often obscured the nuclei. Pharmacological agents that increase intracellular cAMP prevented degranulation, whereas those that increase cGMP had no effect on degranulation. Colchicine inhibited degranulation but did not interfere with the phagocytosis of staphyloccoci. Endotoxin-activated serum, ECF-A, phytohemagglutinin, concanavalin A, levamisole, and compound 48/80 caused degranulation of eosinophils per se. The presence of disodium cromoglycate prevented this degranulation. Compound 48/80 and disodium cromoglycate had no effect on the level of intracellular cAMP and cGMP.

Chemotactic Factors↗
PubMed1981

Production of a suppressor factor by adherent cells from Mycobacterium tuberculosis-infected guinea-pigs.

Adherent cells from the spleen of guinea-pigs infected with Mycobacterium tuberculosis (M. tuberculosis) spontaneously released a factor which suppressed the blastogenic response of normal guinea-pig and human peripheral blood lymphocytes to PHA activation. Suppressor factor production was evident within 3 hr of culture, continued for 2 days and diminished thereafter. This effect was not observed in supernatants derived from normal guinea-pig splenic adherent cells or from peripheral blood adherent cells of both normal or M. tuberculosis-infected guinea-pigs. Analysis of the spontaneously generated adherent cell supernatant indicated that it activated a subpopulation of lymphocytes to become suppressor cells. We conclude that adherent cells phagocytosing M. tuberculosis at the site of the lesion release a factor which activates suppressor cells, and that these cells may be important in the cellular unresponsiveness which develops in animals or man with advanced tuberculosis.

Animals↗
PubMed1981

Production of a suppressor factor by human adherent cells treated with Mycobacterium tuberculosis: absence in systemic lupus erythematosus.

When human peripheral blood mononuclear cells are activated by mitogens in the presence of Mycobacterium tuberculosis (M. tuberculosis), considerable suppression of 3H-thymidine incorporation is observed. Proliferation of mononuclear cells from patients with SLE was not suppressed by treatment with mycobacteria. Analysis of suppressor effect indicated that normal peripheral blood adherent cells treated with mycobacteria release a soluble factor which activates a precursor cell population to become active suppressor T cells. Although lymphocytes from patients with SLE were responsive to suppressor factor produced by normal adherent cells treated with mycobacteria, SLE adherent cells were incapable of producing suppressor factor when treated in the same way. In order to determine whether the inability of SLE adherent cells to produce suppressor factor was due to the presence of immune complexes on the surface of these cells, SLE adherent cells were trypsinized or preincubated prior to treatment with mycobacteria. Neither of these manoeuvres restored the ability of SLE adherent cells to produce suppressor factor. Furthermore, normal adherent cells continued to produce the factor after prior treatment with varying concentrations of human serum albumin-anti-human serum albumin complexes. The results suggest that a basic adherent cell defect exists in SLE and that under certain circumstances this may give rise to a secondary defect of suppressor cell activation.

Adolescent↗
PubMed1981

The in vivo and in vitro effects of levamisole in patients with lepromatous leprosy.

Levamisole, 150 mg daily, was administered on 2 consecutive days per week for 6 weeks to two groups of patients with lepromatous leprosy. Group I was composed of patients who were receiving specific anti-leprosy therapy for varying periods of time and Group II were untreated lepromatous patients. Whereas half the patients in Group I received levamisole and the other half a placebo, those in Group II all received levamisole. Patients in both groups showed a) no clinical improvement, b) no conversion of the lepromin reaction, c) no histological change in skin biopsies, d) conversion of SKSD skin reactions from negative to positive in 20% of patients from each group, and e) unaltered absolute neutrophil counts. Whereas the total lymphocyte counts were unchanged in patients from Group I, 13 patients from Group II showed an increased lymphocyte count of greater than 10%. Lymphocyte transformation and lymphokine production in the second group showed no significant change, although four patients showed some lymphokine production after levamisole therapy. E and EAC rosettes were significantly increased in cases where these were reduced prior to treatment with levamisole-Side effects due to levamisole were not experienced.

Adolescent↗
PubMed1980

In vitro effects of histamine on eosinophil migration.

Histamine at concentrations of 5 X 10(-6) to 5 X 10(-5) M increased eosinophil movement to endotoxin-activated serum (EAS). This effect was due entirely to stimulation of random migration (chemokinesis). Directional motility (true chemotaxis) was inhibited by these concentrations. Regulation of chemotaxis was apparently mediated via an H2 receptor as metiamide, an H2 receptor antagonist, but not diphenylhydramine hydrochloride, an H1 receptor antagonist, blocked the histamine-induced inhibition of chemotaxis. Both histamine and metiamide when used alone had no effect on eosinophil motility. The histamine effects on motility were associated with increased levels of intracellular cAMP, whereas cGMP levels were not affected.

Cell Movement↗
PubMed1980

Production of a suppressor factor by human adherent cells treated with mycobacteria.

Human peripheral blood mononuclear cell (MN) proliferation and lymphokine production induced by mitogen could be inhibited by heat killed whole mycobacteria. The inhibition was induced by a wide variety of mycobacteri but not by other Gram-positive or Gram-negative organisms or by latex particles. Proliferation and lymphokine production by adherent cell-depleted lymphocytes was not inhibited by these organisms. Adherent cells treated with mycobacteria had the ability to inhibit lymphocyte blastogenesis when co-cultured with the lymphocytes. the inhibitory effect of these adherent cells was due to the release of a heat stable, nondialyzable suppressor cells. These latter cells, which were T gamma cells, could inhibit the blastogenic ability of normal lymphocytes activated by mitogens. The results suggest that in situations of high mycobacterial load, adherent cells are activted to release a suppressor factor that will activate lymphocytes to become suppressor cells. This mechanism may explain the anergy associated with lepromatous leprosy or advanced tuberculosis.

Cell Adhesion↗
PubMed1980

The effects of a soluble factor released by sensitized mononuclear cells incubated with S. haematobium ova on eosinophil migration.

Incubation of sensitized mononuclear cells from patients with schistosomiasis with specific antigen containing a suspension of viable Schistosoma haematobium ova resulted in the release of a soluble factor which was chemotactic for eosinophils. Production of this substance was detectable at 24 h and demonstrated peak chemotactic activity after 2 days in culture. The chemotactic potential was dose-dependent and attracted eosinophils obtained from patients with schistosomiasis or allergic diathesis. Human neutrophil motility was unaffected by this chemoattractant. Preliminary studies demonstrated that the chemotactic factor is a heat-stable substance with peak activity associated with a molecular weight of approximately 42,000. These findings may reflect an in vitro correlate of cell-mediated immunity and may indicate a role played by the lymphocyte in the control of eosinophil function in human biology.

Antigens↗
PubMed1978

Staining of eosinophil granulocytes in chemotactic studies.

A fast and reproducible method for the staining of eosinophils on millipore filters for the study of chemotaxis is described. This procedure allows for the easy differentiation of eosinophils from other granulocytes both at the intra-filter level and on the filter surface.

Chemotaxis, Leukocyte↗