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M Haak-Frendscho

Publications and source records attributed to M Haak-Frendscho.

52 records · Page 3Linked to original sources
PubMed1992

Use of recombinant interleukin-2 to enhance adoptive transfer of resistance to Listeria monocytogenes infection.

In vitro incubation of Listeria-immune spleen cells (LISC) with recombinant interleukin-2 (rIL-2) for at least 3 days increased their ability to transfer antilisteria resistance to recipient mice. This effect was blocked by the in vitro addition of transforming growth factor beta 1. The level of protection afforded by the transfer of rIL-2-incubated LISC was further elevated by the in vivo administration of rIL-2 at a dose that by itself did not significantly increase antilisteria resistance. The antilisteria resistance of recipient mice remained elevated for approximately 7 days and then rapidly declined to undetectable levels by 10 days. After cell transfer, recipient mice were protected against challenge with Listeria monocytogenes but not Salmonella typhimurium, Yersinia enterocolitica, or Streptococcus pyogenes. Flow cytometric analyses revealed an increase in the percentages of CD8+, NK+, and gamma delta T cell receptor+ cells but no change in the percentage of CD4+ cells as a result of LISC coculturing with rIL-2. In vitro depletion of CD4+ cells just prior to transfer had no significant effect on the adoptive transfer of resistance; depletion of CD8+ cells reduced the level of resistance by approximately 25%. Combined depletion of Thy-1.2+, CD4+, and CD8+ cells just prior to adoptive transfer diminished the level of protection in the spleens but not the livers of recipient mice. These data suggest that rIL-2 can be used to augment adoptive immunotherapy for bacterial infection in a manner similar to adoptive immunotherapy of human cancer patients. Although the protective cell population was not definitively identified, it appeared to be independent of CD4+ cells and only partly dependent on CD8+ cells.

Animals↗
PubMed1991

rIL-1 alpha enhances adoptive transfer of resistance to Listeria monocytogenes infection.

We have previously demonstrated that administration of recombinant rIL-1 alpha enhances resistance against Listeria monocytogenes infection in mice. In this study we considered the possibility that this cytokine might also augment adoptive immunity conferred by the transfer of listeria-immune spleen cells. Concomitant administration of rIL-1 alpha with large numbers (2 x 10(7) or 10(8)) of listeria-immune spleen cells reduced the protection mediated by the transferred cells. Conversely, rIL-1 alpha co-administered with suboptimal numbers (1-5 x 10(6)) of immune splenocytes augmented anti-listeria resistance in an additive fashion. Although transfer of 10(6) listeria-immune spleen cells alone did not result in significant protection, when 10(6) immune cells were incubated with rIL-1 alpha prior to transfer they conferred significant protection to naive recipients. Time course experiments indicated that the greatest protection was achieved when listeria-immune spleen cells were pretreated with rIL-1 alpha for 2 h prior to adoptive transfer. The protection transferred by 10(6) rIL-1 alpha-pretreated immune spleen cells was not inhibited by TGF beta. This study is the first to use rIL-1 alpha to potentiate the adoptive transfer of resistance to an infectious agent by immune cells.

Animals↗
PubMed1990

Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing.

Transforming growth factor beta-1 (TGF-beta) is a multi-potent immunoregulatory peptide that has effects on numerous cell types. Here we report that human TGF-beta inhibits the activation of the macrophage cell line RAW 264.7 for killing of the L1210 tumour cell line. RAW 264.7 cells, like normal macrophages, require sequential interaction with priming and triggering stimuli for full activation of cytolytic activity. TGF-beta inhibits this cytotoxicity in a dose-dependent manner at both the priming and the triggering stage. Addition of as little as 1 ng/ml TGF-beta when added with either the priming signal, recombinant interferon-gamma (IFN-gamma), or the triggering signal, bacterial lipopolysaccharide (LPS), completely abrogated tumouricidal activity. Incubation with TGF-beta also inhibited the morphological changes normally observed in activated RAW 264.7 cells. However, TGF-beta was unable to inhibit the cytotoxic activity of RAW 264.7 cells against the target cell line WEHI 164, which is sensitive to tumour necrosis factor. In contrast to the effects on cytotoxic activity, the cytostatic activity of activated RAW 264.7 cells was not inhibited by TGF-beta at doses of up to 5 ng/ml. In addition, pretreatment of the L1210 target cells with TGF-beta made them refractory to both the cytostatic and cytotoxic effects of RAW 264.7 cells. These data suggest that TGF-beta may be an important mediator in the regulation of macrophage tumouricidal activity.

Animals↗
PubMed1989

Treatment of mice with human recombinant interleukin-2 augments resistance to the facultative intracellular pathogen Listeria monocytogenes.

The effects of exogenously administered human recombinant IL-2 (hrIL-2) on resistance to Listeria monocytogenes infection were examined. Intravenous injection of hrIL-2 significantly enhanced antibacterial resistance in both BDF1 and C3H/HeJ mice. The beneficial effect of hrIL-2 was observed with as little as 0.6 micrograms per mouse, whereas optimum protection occurred at 6 micrograms per mouse, hrIL-2 was equally protective when administered concomitant with the listeriae or up to 24 h prior to infection; it had little effect if given after the bacterial challenge. Kinetic experiments indicated that both the peak bacterial burden and the time lag before L. monocytogenes began to be cleared from the spleen and liver were reduced in hrIL-2-treated mice as compared with control mice. Histopathological examination of spleens and livers confirmed that hrIL-2-treated Listeria-infected mice experienced considerably less damage to these organs than did control mice. Spleen cells from Listeria-infected mice exhibited depressed levels of mitogen-induced proliferation coincident with the peak bacterial burden in the spleen and liver and during the subsequent recovery from the infection. Administration of hrIL-2 to uninfected mice had no effect on spleen cell proliferation in response to mitogens in vitro, nor did hrIL-2 treatment restore normal levels of splenocyte proliferative responses to Listeria-infected mice. In addition, hrIL-2 treatment resulted in attenuated levels of serum colony-stimulating activity in infected mice as compared with control infected mice. Coadministration of both hrIL-2 and human recombinant interleukin-1 alpha at various dose and time combinations had no detectable additive or synergistic effect. Although these data do not suggest an obvious mechanism of action, they clearly demonstrate that hrIL-2 can augment host defense against the facultative intracellular pathogen L. monocytogenes.

Adjuvants, Immunologic↗
PubMed1989

Purification and further characterization of human mononuclear cell histamine-releasing factor.

We have purified and further characterized a histamine releasing factor (HRF) derived from human mononuclear cells using gel-filtration HPLC, reverse-phase HPLC, anion exchange chromatography, and elution from SDS gels after electrophoresis. Considerable heterogeneity is seen, far exceeding that published in prior reports. Gel filtration HPLC yielded a major peak at molecular weight 30,000 and minor peaks at 50,000 and 12,000. Reverse-phase HPLC gave one major fraction in the void volume and an eluted peak at 50-60% acetonitrile. Accell QMA anion exchange HPLC revealed three peaks of activity; one in the void volume similar to that published previously using QAE-Sephadex, and peaks that eluted at 0.5 and 0.8 M ammonium acetate, respectively. Electroelution following SDS-PAGE yielded peaks at MW 12,000 and 15-17,000 plus variable peaks at 25-27,000, 31-34,000, and 80-90,000 D. Using a combination of the aforementioned procedures, we have purified molecular species of HRF at 41,000 and 17,000 D to apparent homogeneity, as judged by SDS PAGE and autoradiography. Since human interleukin 3 and granulocyte-macrophage colony-stimulating factor possess histamine-releasing capability, it is clear that multiple cytokines can share this activity. However, the major HRF we isolate from human mononuclear cells appears, thus far, to be unique.

Biomarkers, Tumor↗
PubMed1989

Relationship of human macrophage agglutination factor to other fibronectins.

Human macrophage agglutination factor (MAggF) is a lymphokine with a number of biochemical and immunochemical similarities to the fibronectins (FN). The present study was undertaken to define this relationship more exactly. Peripheral blood mononuclear cells (PBMC) and cloned human CD4+T-cell lines synthesized both MAggF and immunoreactive FN de novo following antigen or mitogen activation. MAggF produced under those conditions co-purified with an immunoreactive FN on gelatin-affinity and gel-filtration chromatography. This FN had a consistently slightly smaller relative molecular mass than plasma FN on both immunoblotting and gel filtration. Purified human MAggF was extremely active: it agglutinated human monocytes at fM concentrations and was up to 2,000,000 times more active in agglutinating mononuclear phagocytes than other purified FN. The action of MAggF on monocytes was dependent on at least two antigenically distinct cell-surface FN receptors. We suggest that the extreme activity of MAggF is a result of co-operative interactions between FN domains on the MAggF molecules and multiple distinct classes of FN receptors on responding cells.

Animals↗
PubMed1988

Neutrophils and mast cells. Comparison of neutrophil-derived histamine-releasing activity with other histamine-releasing factors.

Human neutrophil-derived histamine-releasing activity (HRA-N) was partially purified and found to contain a heat-stable 1400 to 2300-Da fraction which caused human basophils and rat basophil leukemia cells (RBL) to degranulate. The capacity of HRA-N to activate basophils was not related to the gender or atopic status of the basophil donor, but was related to anti-IgE responsiveness. Several lines of evidence suggest that HRA-N and anti-IgE induce histamine release through distinctly different mechanisms: 1) the time course of HRA-N- and anti-IgE-induced RBL histamine release are different; 2) HRA-N causes histamine release from RBL with and without surface-bound IgE; 3) lactic acid stripping of IgE from human basophils reduces anti-IgE-induced histamine release, but has no consistent effect on HRA-N-induced histamine release; and 4) passive sensitization of lactic acid-stripped basophils with IgE restores anti-IgE-induced histamine release but not HRA-N-induced histamine release. Several histamine-releasing factors (HRF) were compared with HRA-N. Human nasal HRF (HRF-NW, crude and partially purified fractions of 15 to 30, 3.5 to 9, and less than 3.5 kDa), like HRA-N, caused equal histamine release from both native and IgE-sensitized RBL. However, only the 15- to 30-kDa fraction caused histamine release from human basophils in the doses tested. Mononuclear cell HRF (HRF-M, crude and a partially purified 25 kDa Mr fraction) and platelet HRF (HRF-P, crude preparation) failed to cause histamine release from either native or IgE-sensitized RBL but caused 30 +/- 5.5% and 20 +/- 10% net histamine release from human basophils, respectively. HRA-N and HRF-NW were both stable to boiling. These data, taken together, suggest that the capacity of HRA-N to induce RBL and human basophil histamine release and of HRF-NW to stimulate RBL histamine release is independent of IgE. The data further suggest that HRA-N and HRF-NW can be distinguished by size, and that they both differ from mononuclear cell HRF and platelet HRF. Thus, it appears that inflammatory cells generate a family of distinct HRF.

Animals↗
PubMed1988

Responsiveness to human mononuclear cell-derived histamine-releasing factor. Studies of allergic status and the role of IgE.

Human mononuclear cell-derived histamine-releasing factor (MNC-HRF) has m.w. of 29,000 and 23,000 and two charge species isoelectric at pH 6.9 and 7.3. Minor forms of HRF are also seen at m.w. of 12,000 to 15,000 and 60,000 to 80,000. In this manuscript we have further defined the response of human basophils to MNC-HRF in terms of atopic status of cell donors and the role of IgE antibody. We found that basophils of allergic persons, nonallergic controls, or donors who have positive skin tests but no symptoms, cannot be distinguished based upon responsiveness to HRF. Further, the response of basophils that have been desensitized to anti-IgE is retained when they are subsequently stimulated with HRF derived from human MNC. Thus an interaction with cell-surface IgE to cause histamine release is not evident. Nevertheless, one of two IgE myeloma proteins tested were capable of binding HRF and such binding could be utilized as a purification step. We conclude that MNC-HRF is heterogeneous in terms of size, charge, and affinity for a subpopulation of IgE. Histamine release is more prominent in atopic individuals but does not appear to require an interaction with IgE.

Basophils↗
PubMed1988

Comparison of mononuclear cell and B-lymphoblastoid histamine-releasing factor and their distinction from an IgE-binding factor.

We have characterized the histamine-releasing factors (HRF) from a B-lymphoblastoid cell line (RPMI 8866), compared it to mononuclear cell-derived HRF, and distinguished these from the IgE-binding factor produced by RPMI 8866. The B-cell-derived HRF fractionates at molecular weights of 90,000, 70,000, and 12-15,000 while mononuclear cell HRF has a major component at 24-26,000. The isoelectric points for B-cell HRF are 6.2-6.3 and 6.6-6.8 in contrast to 6.9 and 7.3 for mononuclear cell-derived HRF. The kinetics of histamine release by either HRF was the same, with half-maximal release in 5-10 min, unlike the rapid release caused by anti-IgE. Since HRF has been reported to be an IgE-binding factor, we screened column fractions for the IgE-binding factor secreted by RPMI 8866; this is known to be a shed low affinity IgE receptor. The chromatographic pattern and isoelectric point of this IgE-binding factor does not correspond to HRF; the purified IgE-binding factor had no significant histamine releasing activity on human basophils, and neither source of HRF was reactive in a radioimmunoassay to the IgE-binding factor. Our data suggest that HRF is quite heterogeneous and varies in physiochemical properties depending upon the cell source. The molecular relatedness (or nonrelatedness) of those HRFs is unclear; however, our data indicate that although HRF or fractions therefrom may bind to IgE as has been reported, it is unrelated to the low affinity IgE receptor.

B-Lymphocytes↗
PubMed1988

Recombinant human interleukin-1 beta causes histamine release from human basophils.

Histamine releasing factors (HRFs) have been demonstrated to be secreted by human lymphocytes and monocytes (alveolar macrophages); however, none has been purified to date. Because of the similarity of our HRF to the physical chemical properties of interleukin-1 (IL-1) and tumor necrosis factor (TNF), we have assessed the ability of preparations of IL-1 and TNF to cause basophil histamine release (HR). Human recombinant pro-IL-1 beta, recombinant mature IL-1, and, to a lesser extent, human recombinant TNF caused significant HR from a subpopulation of donor basophils. The pro-IL-1 beta elicited a dose response between 40 and 800 ng/ml; higher concentrations were inhibitory. Approximately 30% of subjects tested are responsive to either mature IL-1 or TNF. These share the same responder subset, but the magnitude of the TNF response is considerably less. A response to the pro-IL-1 was restricted to those subjects with prominent HR to anti-IgE; the response to mature IL-1 and TNF was unrelated to the response to anti-IgE. As in other functional assays, the pro-IL-1 is 50- to 100-fold less potent than mature IL-1, and unlike human HRF, it is highly unstable and rapidly loses activity. Mononuclear cell-derived HRF differs in physicochemical properties from IL-1 or TNF; nevertheless, it appears likely that a variety of cytokines may possess histamine-releasing capability.

Antibodies, Anti-Idiotypic↗
PubMed1988

Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release.

Histamine-releasing factors (HRFs) have been shown to be released from a variety of human cells, including T lymphocytes and alveolar macrophages. We considered the possibility that known cytokines might possess such activity on human basophils and/or mast cells and therefore tested preparations of human recombinant IL 3, IL 4, IL 5, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon a panel of basophil donors. IL 3 and GM-CSF possessed significant histamine-releasing activity in 8 of 10 and 12 of 14 subjects, respectively. In each instance, a dose response could be demonstrated. IL 4 and G-CSF had no such activity, whereas IL 5 had activity in only 2 of 14 donors tested. We conclude that IL 3 and GM-CSF represent two effective HRFs, and suggest that HRF, as isolated based upon histamine-releasing activity, is likely to be heterogeneous in terms of molecular identity. Whether previously described HRFs relate specifically to IL 3 or GM-CSF must await primary sequence analysis of HRF and/or studies with monospecific antisera.

Basophils↗
PubMed1986

Concurrent production of macrophage agglutination factor and factor VII by antigen-stimulated human peripheral blood mononuclear cells.

We have studied concurrent production of macrophage agglutination factor (MAggF) and procoagulant activity by antigen-stimulated human blood mononuclear cells to gain insight into biochemical mechanisms underlying delayed hypersensitivity inflammatory reactions. After stimulation of cells from tuberculin-sensitive donors with tuberculin, MAggF was present in culture supernatants while the overwhelming majority of procoagulant activity remained cell-associated. Neither MAggF nor procoagulant activity was found in reconstituted control cultures, nor in tuberculin-stimulated cultures of non-sensitive cells. Concanavalin A and lipopolysaccharide elicited both activities from cultured mononuclear cells, regardless of donor sensitivity. Human MAggF bound to insolubilized gelatin, heparin and a monoclonal anti-fibronectin (FN) antibody, and its activity was inhibited by another monoclonal antibody directed against the gelatin-binding domain of FN. Treatment of indicator peritoneal exudate cells with monoclonal anti-FN receptor antibody inhibited their response to human MAggF. These results suggest that human MAggF, like the analogous guinea-pig activity, is FN-associated. Antigen-elicited procoagulant activity shortened the recalcification time of normal, factor VII- and factor IX-deficient plasma, partially corrected prothrombin times of factor VII-deficient plasma, had no effect on recalcification and prothrombin items of factor X- and factor V-deficient plasma, and was inhibited by specific anti-factor VII antibody. Thus, human mononuclear cell procoagulant consists of both tissue factor and factor VII, whether it is induced by antigen or mitogen. Antigen-stimulated blood mononuclear cells are able to provide a signal for local fibrin deposition and a protein mediating fibrin binding to mononuclear phagocytes and collagen at sites of delayed hypersensitivity reactions.

Animals↗
PubMed1985

A histamine-releasing factor from activated human mononuclear cells.

Human mononuclear cells activated by streptokinase-streptodornase have been shown to elaborate a factor capable of releasing histamine from human basophils. We have developed reproducible methods for its production in large quantities by using cells obtained from leukapheresis packs, by detection utilizing donor basophils known to release well with anti IgE, and by quantitation of histamine by the radioenzyme method. Human histamine-releasing factor (HRF) gave a single peak upon gel filtration with an estimated m.w. of 32,000; SDS gel electrophoresis revealed a single major band as seen at m.w. 30,000. HRF can be resolved into at least two forms separable by ion-exchange chromatography on QAE Sephadex, and two peaks of activity were obtained by chromatofocusing or isoelectric focusing in gels at pH 6.9 and between 7.4 and 8.3. This factor represents an important potential link between cellular immunity and immediate hypersensitivity.

Basophils↗
PubMedDate not supplied

Allergen-induced sensory neuroplasticity in airways.

This study investigates the influence of allergic inflammation in airway sensory innervation. We conclude that allergic inflammation in the guinea pig leads to both an increase in excitability, as manifested by an increase in the mechanical sensitivity of the airway nerve endings, and an induction of substance P production in airway sensory neurons. The data are consistent with the hypothesis that the induction of substance P occurs in fast conducting nodose sensory neurons that were previously devoid of this neuropeptide. Thus, allergen challenge is associated with a phenotypic change in the airway tachykinergic innervation. We also provide evidence that nerve growth factor is a potentially important mediator for these effects, and that it is elevated in the bronchoalveolar lavage of asthmatic subjects.

Allergens↗