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H D Flad

Publications and source records attributed to H D Flad.

277 records · Page 16Linked to original sources
PubMedDate not supplied

Activation of human monocytes by interleukin 2: role of T lymphocytes.

The effect of interleukin 2 (IL2) on the capability of human monocytes to secrete reactive oxygen species triggered via Fc-gamma receptor (Fc-gamma R) function had been investigated by measurement of chemiluminescence (CL). IL 2 did not activate highly purified (hp) monocytes to respond to Fc-gamma R mediated phagocytic stimulation with an enhanced respiratory burst activity unless low numbers of T cells had been co-cultured with hp monocytes. Supernatants from IL 2 treated PBMC contained interferon-gamma (IFN-gamma) and monocyte activating factor (MAF) activity. The secretion of both cytokine activities was strongly enhanced by cooperative function of monocytes. The correlation of IL 2 induced secretion of IFN-gamma and MAF activity was striking, however, monoclonal antibody (mAb) anti-human IFN-gamma failed to abrogate IL 2 stimulated and lymphocyte dependent monocyte activation. Although IL 2 had no direct monocyte activating effect, pretreatment of hp monocytes with IL 2 led to monocyte priming: subsequent co-culture with autologous control T cells enhanced the monocyte Fc-gamma R mediated CL response. The priming of monocytes by IL 2 was dependent on the interaction of IL 2 with the monocytic IL 2 receptor as shown by inhibition experiments with anti IL 2 R monoclonal antibody. Thus the IL 2 driven monocyte/T-cell interaction leads to an increased Fc-gamma R mediated monocytic respiratory burst activity and to the secretion of a soluble MAF activity, but there were no detectable amounts of IFN-gamma.

Antibodies, Monoclonal↗
PubMedDate not supplied

An examination of the immune system of the duck (Anas platyrhynchos) for factors resembling some defined mammalian cytokines.

Duck lymphoblasts generated by phytohaemagglutinin (PHA) did not respond to recombinant or Jurkat cell line human interleukin (IL)-2 or possess surface antigens resembling mammalian IL-2 receptors or IL-1 beta. Supernatant fluids from normal and PHA-stimulated duck lymphocyte cultures, and normal and lipopolysaccharide (LPS)-stimulated monocytes, gave negative results in a range of assays for biological activity and immunochemical presence of factors resembling mammalian IL-1 and IL-2. However, supernatant fluids from LPS-stimulated duck monocytes contained IL-6-like activity (up to 35 units/mL) assessed on the 7TD-1 murine cell line. We were unable to demonstrate mRNA that would hybridize to cDNA probes for human IL-1 beta, IL-6, and tumour necrosis factor (TNF) in extracts of blood and lymphoid organs from normal and antigen-stimulated ducks. Because homologous serum or plasma is essential for duck lymphocytes and macrophages to respond to mitogens in vitro, we asked whether this growth-factor-like activity might be caused by substances resembling mammalian cytokines. Serum and plasma were examined for activity consistent with IL-1 and IL-6 on mammalian target cells. None was detected. Instead, both serum and plasma contained inhibitors of human IL-1 beta and IL-6, detected at dilutions up to 1:100. Inhibition by serum was heat (56 degrees C, 30 min) labile but inhibition by plasma was heat stable. The identities and biological functions of these inhibitors remain to be defined.

Animals↗
PubMedDate not supplied

Chemical structure and biologic activity of bacterial and synthetic lipid A.

The chemical structure of the lipid A component of enterobacterial lipopolysaccharide (LPS) is now known in some detail. For example, lipid A of Escherichia coli consists of a beta(1----6)-linked D-glucosamine disaccharide that carries four (R)-3-hydroxytetradecanoyl groups in positions 2, 3, 2', and 3' and two phosphoryl residues in positions 1 and 4'. The hydroxy fatty acids at positions 2' and 3' are acylated at their 3-hydroxyl groups by dodecanoic acid and tetradecanoic acid, respectively. The hydroxyl groups in positions 4 and 6' are free, the latter serving as the attachment site for the polysaccharide component in intact LPS. On the basis of this structure, E. coli-type lipid A and partial structures thereof have been chemically synthesized (group of T. Shiba, Osaka University, Osaka, Japan) and analyzed for endotoxic activity. In all in vivo and in vitro test systems employed (including lethal toxicity, pyrogenicity, local Shwartzman reactivity, B lymphocyte mitogenicity, macrophage activation, and serologic cross-reactivity with lipid A antiserum), synthetic lipid A has activity identical to that of E. coli lipid A. These findings support the structural proposal for lipid A and prove the previous hypothesis that the endotoxic principle is embedded in lipid A.

Animals↗
PubMedDate not supplied

The role of monocytes in the induction and regulation of IFN-gamma production by lectin-activated human T lymphocytes.

The data presented show that the production of interferon gamma (IFN-gamma) by pokeweed mitogen (PWM)-activated T lymphocytes requires monocytes and that the amount of lymphokine produced depends on the number of monocytes present in the culture. Accessory function of monocytes was independent from their ability to secrete IL-1 but required cell-cell contact, since blocking of adhesion molecules reduced the IFN-gamma production. Furthermore, production of IFN by lectin-preactivated T lymphocytes could not be triggered by IL-2 but also required monocyte-T cell interaction.

Cell Communication↗
PubMedDate not supplied

rIL-2-activated killer cell generation is influenced by autologous TNF-alpha production.

Low-density (LD) lymphocytes and their CD16+ and CD16- subsets were cultured with recombinant interleukin-2 (rIL-2) in the presence or absence of tumor necrosis factor-alpha (TNF-alpha)-neutralizing antibodies (Abs). Cultures were evaluated with respect to the cell recovery, K562 cytolytic potential and interferon (IFN)-gamma production. The addition of anti-TNF-alpha neutralizing Abs to rIL-2-activated cultures of LD lymphocytes resulted in greater cell expansion and a decrease in cytolytic potential. In the CD16+ subpopulation of LD lymphocytes, there was an increase in cytolytic potential and no improvement in the cell yield was observed. The CD16- subpopulation of LD lymphocytes was not affected by the Abs. In cultures with anti-TNF alpha Abs (polyclonal or monoclonal), a decrease in the rIL-2-dependent generation of IFN-gamma was observed. Recombinant TNF-alpha, when added to rIL-2-supplemented cultures of LD lymphocytes, enhanced the rIL-2-induced generation of IFN-gamma in a dose-dependent manner. TNF-alpha appeared to up-regulate rIL-2-induced IFN-gamma production by LD lymphocytes and to modulate lymphokine-activated killer cell generation (neutralization of TNF-alpha promoted cell expansion in LD lymphocyte cultures and cytotoxicity in CD16+ lymphocyte cultures).

Antibodies, Monoclonal↗
PubMedDate not supplied

Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells.

The expression and functional role of dipeptidyl peptidase IV (DP IV, CD26, EC 3.4.14.5) was studied on human natural killer (NK) cells. Here we show that freshly isolated NK cells do express only low amounts of DP IV. However, after IL-2 stimulation of NK cells (70% purity) surface DP IV expression was significantly increased in a subpopulation (30%) of these cells. Specific DP IV inhibitors (Lys-[Z-(NO2)]-piperidide, Lys-[Z(NO2)]-thiazolidide) and polyclonal antibodies directed against the ectopeptidase suppressed DNA synthesis and cell cycle progression of NK cells. The natural cytotoxic activity of DP IV+ CD56+ cells was found unchanged in comparison to those of DP IV- CD56+ cells. DP IV inhibitors had no effect on the natural cytotoxicity of mononuclear cells. From these data we conclude that DP IV is involved in the regulation of proliferation of NK cells, whereas natural cytotoxicity seems to be regulated independently.

Cell Cycle↗