Search PubMed⌕ Search

Biomedical subjects

H G Remold

Publications and source records attributed to H G Remold.

At least 55 records · Page 3Linked to original sources
PubMed1988

IFN-gamma, tumor necrosis factor-alpha, and urokinase regulate the expression of urokinase receptors on human monocytes.

The ability of macrophages to reach inflammatory loci is crucial in the function of cellular immunity. Invasive properties of macrophages may be due to the proteinase urokinase which binds to cell surface receptors, and thereby confers on macrophages the capacity for localized proteolysis of the interstitium. Here, we investigated the role of the macrophage-activating factors IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF and of urokinase on the expression of urokinase receptors by human cultured monocytes. IFN-gamma and TNF-alpha induced increased urokinase binding to human cultured monocytes in a time- and dose-dependent fashion. At optimal concentrations, IFN-gamma (200 U/ml) increased the number of receptors/cell from 14,000 to 64,000, TNF-alpha (50 U/ml) to 30,000, and combinations of IFN-gamma and TNF-alpha to 90,000. Granulocyte-macrophage-CSF had no effect. The enhanced urokinase binding is due to increased numbers of urokinase receptors and not an increased affinity of the receptor for urokinase. In the presence of urokinase during monocyte activation, IFN-gamma induced only 25,000 receptors/cell. However, urokinase does not inhibit increased receptor expression when the cells are activated with TNF-alpha. The effect of urokinase on induction of urokinase receptors by combinations of IFN-gamma and TNF-alpha varied with the dosage of TNF-alpha: A combination of IFN-gamma (200 U/ml) and TNF-alpha (15 U/ml) induced 38,000 receptors/cell in the presence and 90,000 receptors/cells in the absence of urokinase, whereas IFN-gamma (200 U/ml) and TNF-alpha (20 U/ml) induced 90,000 receptors/cell in the absence and presence of urokinase. These studies demonstrate that IFN-gamma, TNF-alpha, and urokinase collectively regulate the number of urokinase receptors on human monocytes. The induction of urokinase receptors may be responsible for increased invasiveness of the activated macrophage.

Binding, Competitive↗
PubMed1988

Identification and characterization of a non-interferon antileishmanial macrophage activating factor (antileishmanial MAF).

A non-interferon lymphokine elaborated from PHA and Con A-stimulated human T-cell hybridoma, T-CEMA, has been found to activate monocyte-derived macrophages for the intracellular killing of L. donovani (antileishmanial MAF). This T-cell hybridoma derived antileishmanial MAF which has an apparent mw of 65,000 and pI of 5.3-5.6, contains neither antiviral activity nor colony stimulating activity. Furthermore, antileishmanial MAF is not neutralized by anti-MIF, anti-IFN-gamma or anti-GM-CSF antibodies.

Animals↗
PubMed1988

Cytokine activation of antibacterial activity in human pulmonary macrophages: comparison of recombinant interferon-gamma and granulocyte-macrophage colony-stimulating factor.

We examined the ability of two recombinant human cytokines, granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF) and interferon-gamma (rHu-IFN-gamma) to activate antibacterial mechanisms in human pulmonary macrophages (PM) and peripheral blood monocytes (PBM). Growth of Legionella pneumophila (LP) was assessed in PM or PBM which had been exposed to either rHu-IFN-gamma (500-1000 u/ml) or rHu-GM-CSF (1 to 10,000 u/ml). In both PM and PBM exposed to 500 u/ml rHu-IFN-gamma, growth of LP was reduced compared to cells exposed to media alone. By comparison, exposure of these cell types to rHu-GM-CSF had no detectable effect on bacterial replication. In order to investigate potential mechanisms accounting for this observation, the effect of these cytokines on the hydrogen peroxide (H2O2)-releasing capacity of cells was studied. Exposure of PM and PBM to rHu-IFN-gamma (500 to 1000 u/ml) resulted in increased production of H2O2 triggered by phorbol myristate acetate; when subjected to the same experimental conditions, rHu-GM-CSF-exposed cells exhibited no increase in H2O2 production. To further clarify the role of rHu-IFN-gamma-induced augmentation of oxidative metabolism on cellular inhibition of bacterial growth, an amount of catalase capable of completely neutralizing extracellular H2O2 was added to cells before and during infection. This did not abrogate the antibacterial activity of rHu-IFN-gamma. These studies demonstrate that rHu-IFN-gamma but not rHu-GM-CSF is capable of augmenting the capacity of PM and PBM to restrict LP growth. These data suggest that the antibacterial activity of rHu-IFN-gamma in this system may involve oxidative as well as nonoxidative mechanisms.

Bacteria↗
PubMed1988

Human monocyte-derived macrophages are lysed by schistosomula of Schistosoma mansoni and fail to kill the parasite after activation with interferon gamma.

In this study was examined the interaction between schistosomula of Schistosoma mansoni and human monocyte-derived macrophages activated with interferon gamma (IFN-gamma). Peripheral blood monocytes were matured for 6 days and activated by further culture with IFN-gamma (600 U/ml). These IFN-gamma-treated monocyte-derived macrophages are cytotoxic for the tumor cell line K562, which is not killed by nonactivated monocyte-derived macrophages. Activated monocyte-derived macrophages were incubated with schistosomula at ratios of 10(3):1 and 10(4):1 in the presence of serum pooled from patients with schistosomiasis. This antiserum promoted an increased adherence of cells to the parasite. However, the activated monocyte-derived macrophages failed to kill the schistosomula under all conditions tested. On the contrary, the monocyte-derived macrophages were killed by schistosomula in a time-dependent and antibody-dependent manner, which was most evident at a lower effector/target ratio, 200:1. Electron microscopy showed that monocyte-derived macrophages were lysed on the surface of schistosomula. Further, both monocyte-derived macrophages and contaminating blood platelets fused with the parasite surface membrane, so that the cell plasma membrane and the outer tegumental membrane formed a hybrid membrane. The results indicate that matured human monocyte-derived macrophages activated by IFN-gamma are unable to kill schistosomula. Instead, the effector cells fuse with the parasites and are lysed by them.

Animals↗
PubMed1987

Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages.

Recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) obtained from cloned complementary Mo cell DNA and expressed in COS-1 cells activates cultured peripheral blood monocyte-derived macrophages in vitro to become cytotoxic for intracellular L. donovani. The antileishmanial effect of rGM-CSF, which can be completely neutralized by anti-rGM-CSF antiserum, is maximal after 36 h preincubation with the cultured macrophages, compared with that of rIFN-gamma, which reaches its maximum at 72 h of preincubation. The antileishmanial effect of GM-CSF as well as IFN-gamma is independent of detectable amounts of LPS and is not augmented by the addition of 10 or 50 ng/ml of LPS. Simultaneous administration of suboptimal doses of rGM-CSF and rIFN-gamma to monocyte-derived macrophages results in greater antileishmanial activity by these cells than administration of either lymphokine alone, although no enhancement of antileishmanial activity is observed when optimal doses of these two lymphokines are applied together.

Animals↗
PubMed1986

Monocyte procoagulant inducing factor: a lymphokine involved in the T cell-instructed monocyte procoagulant response to antigen.

A T cell-derived lymphokine couples the recognition of alloantigens by human T inducer cells to monocyte effector procoagulant activity (PCA). This collaborative cellular response results in expression of the functional tissue factor gene product and initiation of the extrinsic coagulation protease cascade as an inflammatory sequelae to the immune response. We now provide initial characterization of this lymphokine, provide evidence that it is a unique lymphokine, and designate it as monocyte procoagulant inducing factor (MPIF). MPIF was produced by alloantigen-stimulated, nylon wool-purified T cells and was not diminished by irradiation. MPIF active supernatants induced PCA in isolated monocytes, and the effect was not modified by the presence of T cells with the responding monocytes, consistent with a direct effect on the monocyte effector cells rather than an indirect effect via an intermediate accessory T cell. Full expression of PCA by monocytes was complete within 4 to 6 hours. MPIF activity in mixed lymphocyte culture (MLC) supernatants (MLC-SN) was stable at pH 2.0 for 24 hr, but was diminished after exposure to pH 10.5 for 30 min. MPIF activity was stable at 56 degrees C but was labile at 63 degrees C or higher. When characterized by chromatography on Sephadex G-100 superfine at either pH 7.2 or 3.6, the activity was recovered in a major discrete peak of about 55,000 daltons, and minor peaks of activity at about 14,000 and greater than 150,000 daltons. There was no correlation between the presence or concentration of INF-gamma, INF-alpha, IL 1, IL 2, GM-CSF, CSF-1, TNF-alpha, TNF-beta (lymphotoxin), or migration inhibitory factor (MIF) with MPIF activity. Each of the previously defined cytokines was analyzed directly for MPIF activity. INF-gamma, INF-alpha, GM-CSF, TNF-alpha, and CSF-1 did not possess MPIF activity over a wide range of concentrations. IL 1 and IL 2 lacked activity at concentrations present in MLC medium positive for MPIF; however, at higher concentrations each demonstrated slight activity. There was a poor correlation between MPIF and MIF activities in MLC-SN, and the content of MIF was insufficient to account for the expressed level of MPIF activity. The lack of identity of these cytokines with MPIF was supported by selected MLC medium that lacked IL 1, IL 2, and MIF and yet contained high MPIF activity. MPIF was additionally distinguished from IL 1, IL 2, and MIF on the basis of separation in Sephadex G-100 superfine.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Coagulation Factors↗
PubMed1986

An acidic lymphokine distinct from interferon-gamma inhibits the replication of herpes simplex virus in human pulmonary macrophages.

Supernatants from concanavalin A-stimulated human peripheral blood mononuclear cells were fractionated by gel filtration and isoelectric focusing. A fraction with an isoelectric point of 2.2-3.3 containing macrophage migration inhibition factor activity inhibited the replication of herpes simplex virus type 1 in human pulmonary macrophages and U937 cells. This fraction did not inhibit the replication of herpes simplex virus in human fibroblasts. Moreover, the ability of this lymphokine fraction to inhibit viral growth in macrophages was not neutralized by antibody against interferon-gamma. These findings identify a macrophage specific antiviral lymphokine which is distinct biochemically and immunologically from interferon-gamma.

Cell Line↗
PubMed1986

Deficient responses of pulmonary macrophages from healthy smokers to antiviral lymphokines in vitro.

The antiviral function of pulmonary macrophages obtained by broncholavage of healthy smokers and nonsmokers was studied. Compared with nonsmokers' cells, smokers' macrophages produced significantly more virus during in vitro infection with herpes simplex virus type 1 (HSV-1). Exposure of macrophages to either antiviral macrophage-activating factor or interferon-gamma for 20 hr before infection resulted in diminished production of HSV-1 by both types of macrophages. However, in contrast to smokers' cells, exposure of nonsmokers' macrophages to these antiviral lymphokines totally prevented viral replication. This difference could not be attributed to diminished adsorption of virus to smokers' macrophages or to an increased proportion of extracellular to intracellular virus in smokers' cell cultures. The effect of smoking on viral infectivity did not appear to be mediated by secretion of a soluble factor by the macrophage because incubation of nonsmokers' cells with supernatant from smokers' cell cultures did not affect the growth of HSV-1.

Adsorption↗
PubMed1986

T cell-derived migration-inhibitory factor and colony-stimulating factor share common structural elements.

Migration-inhibitory factor (MIF) is a lymphokine that acts to localize mononuclear phagocytes (monocytes and macrophages) and perhaps to activate them. Mo cells are a human T cell leukemia virus II-infected T cell line previously shown to secrete large quantities of MIF upon stimulation with phytohemagglutinin and phorbol myristate acetate. MIF was purified from Mo cell-conditioned medium by gel filtration, phenyl-Sepharose affinity chromatography, isoelectrofocusing, and reverse-phase high-performance liquid chromatography (RP-HPLC). Overall purification was 6,000-fold. The purified MIF fraction was found to display potent colony-stimulating factor (CSF) activity when assayed on human bone marrow cells. The double peak of MIF activity as shown by C 18-RP-HPLC coincided with the double peak of CSF activity. A monoclonal antibody selected for its anti-MIF activity absorbed both the CSF and the MIF activity. These findings indicate that MIF and CSF are either identical molecules or closely related molecules with common structural elements.

Cell Line↗
PubMed1985

Antigen-dependent heterogeneity of human migration inhibitory factor.

Human migration inhibitory factor (MIF) produced by peripheral blood mononuclear cells stimulated with purified protein derivative, tetanus toxoid, streptokinase-streptodornase, or Candida albicans antigen was analyzed by gel filtration and isoelectrofocusing. In all cases, supernatants harvested after a 24-hr exposure of the mononuclear cells to the antigen yielded only one MIF species with an isoelectric point of 5. In contrast, isoelectrofocusing of supernatants obtained from cells exposed to the antigen for an additional 24 hr demonstrated that different antigens induce the elaboration of different MIF species. Streptokinase-streptodornase and tetanus toxoid induced the production of one MIF species with an isoelectric point of 5 (pH 5-MIF). Stimulation of cells with Candida antigen elaborated a MIF species with an isoelectric point of 3 (pH 3-MIF). In contrast, stimulation of cells with purified protein derivative induced the production of both pH 3-MIF and pH 5-MIF.

Antigens↗
PubMed1985

Generation of human hybridomas producing migration inhibitory factor (MIF) and of murine hybridomas secreting monoclonal antibodies to human MIF.

Human T-cell hybridomas were established by hybridization of concanavalin A (Con A)-stimulated human peripheral blood T lymphocytes with cells from a 6-thioguanine-resistant, aminopterin-sensitive mutant line designated CEM-WH4, derived from the continuously growing human T cell line, CEM. High levels of MIF activity were demonstrated in the supernatants of two hybridoma lines, T-CEMA and T-CEMB but not of CEM-WH4 when stimulated with phorbol myristate acetate and phytohemagglutinin. In comparison, MIF derived from Con A-stimulated peripheral blood mononuclear cells showed 100 times less activity. Upon isoelectrofocusing, MIF activity of T-CEMB was found exclusively between pH 4.6 and 5.3 whereas MIF derived from T-CEMA showed heterogeneity with a major peak of MIF recovered at pH 4.6-5.3 and a minor peak at pH 2.4-3.3. These molecules, however, were all found to have an apparent MW of 68,000 and were resistant to trypsin. Most of these characteristics are in accordance with second day pH 3- and pH 5-MIF derived from peripheral blood mononuclear cells. When spleen cells from BALB/c mice immunized with T-CEMB-MIF were used to fuse with NS-1 mouse myeloma cells, nine hybridomas secreting antibodies to human MIF were obtained. Clone D112 which demonstrated the highest MIF-neutralizing activity was found to neutralize MIF derived from T-CEMA, peripheral blood mononuclear cells, and a T cell line, Mo.

Animals↗
PubMed1985

Partial purification and characterization of a human lymphokine which induces antileishmanial activity in mouse macrophages.

Human blood mononuclear cells stimulated in vitro with concanavalin A secrete a lymphokine which activates mouse macrophages to kill Leishmania enriettii. Supernatants of cells cultivated for 1 day and for 2 days were analyzed for this activity after G-100 gel filtration and isoelectrofocusing. First day antileishmanial activity was found in a MW range of 23,000 with an isoelectric point of 3.6 to 4.0. Second day antileishmanial activity eluted in a peak in the MW range of 23,000 to 65,000 with an isoelectric point of 4.0 to 4.3. This activity could be completely separated from migration-inhibitory factor (MIF) after isoelectrofocusing in first day and in second day supernatants. Antileishmanial activity could be separated from interferon-gamma in first day, but not in second day supernatants.

Antiprotozoal Agents↗
PubMed1985

Glycolipid receptor for human migration inhibitory factor: fucose and sialic acid are important for the human monocyte response to migration inhibitory factor.

The role of carbohydrate in the interaction of human migration inhibitory factor (MIF) with human peripheral blood monocytes was investigated by studying the effects of different exoglycosidases on the cellular response to MIF. When monocytes were pretreated with neuraminidase, an exoglycosidase specific for sialic acid, they became unresponsive to MIF. Other glycosidases, such as beta-galactosidase and alpha-mannosidase, were inactive in this respect. The effect of neuraminidase was reversible since the response to MIF was restored to normal levels after 24 hr. In parallel studies, a glycolipid-enriched extract from U937 cells, a human macrophage-like cell line, known to enhance the monocyte response to MIF, lost this activity when treated with neuraminidase and alpha-L-fucosidase, but not with beta-galactosidase. This suggests the importance of terminal sialic acid and fucose residues for the interaction between monocyte membrane glycolipids and MIF.

Cell Line↗
PubMed1985

Macrophage glycolipid receptors for human migration inhibitory factor (MIF): differentiated HL-60 cells exhibit MIF responsiveness and express surface glycolipids which both bind MIF and convert nonresponsive cells to responsiveness.

The human promyelocytic leukemia line HL-60 when treated with a phorbol diester (TPA) differentiates into cells (HL60-TPA) that respond to human migration inhibitory factor (MIF). Unresponsive HL-60 cells became responsive to MIF when preincubated with a glycolipid-enriched preparation extracted from HL60-TPA cells, human monocytes, human macrophage-like (U937) cell line, or with the purified glycolipid receptor for MIF from guinea pig peritoneal macrophages. Human blood monocytes exhibited an increased response to MIF when preincubated with glycolipids from HL60-TPA and U937 cells but not from HL-60 cells. Finally, glycolipids from HL60-TPA cells but not from HL-60 cells were able to reversibly bind MIF when covalently coupled to agarose. These studies suggest that TPA induces the differentiation of HL-60 cells into MIF-responsive cells through the expression of a glycolipid receptor for MIF.

Cell Differentiation↗
PubMed1984

Glycolipid-dependent interaction between human migration-inhibitory factor and mononuclear phagocytes.

It has been previously established in the guinea pig that the response of peritoneal macrophages to migration inhibitory factor (MIF) is enhanced by a macrophage glycolipid and that gangliosides reversibly bind MIF. This suggests that glycolipids function as cell surface receptors for MIF. In this report, it is demonstrated that the response of human peripheral blood monocytes to human MIF is augmented by preincubation of these cells with glycolipid-enriched material extracted from the human macrophage-like cell line U937 or human peripheral blood monocytes and with a purified glycolipid from guinea pig peritoneal macrophages. In addition, a mixed ganglioside preparation from bovine brain shows the same effect. In contrast, the pure gangliosides, GM1 and GD1a, and glycolipids from the HL-60 cell line, which is a MIF-unresponsive cell line, were not able to enhance the response to human MIF. The specificity of enhancement by particular glycolipids could not be attributed to an increased uptake of only enhancing glycolipids since there was no significant difference between the association of monocytes with radioactive liposomes containing biologically active or inactive glycolipids. Pronase treatment did not affect the enhancing activity of the U937 glycolipid-enriched material. Incubation of cells with glycolipids results in enhancement only if done at 37 degrees C and not at 4 degrees C. Therefore, the association of lipid with the monocyte surface appears to be dependent on temperature. Further evidence for the receptor nature of these enhancing glycolipids is provided by experiments involving affinity purification experiments. Coupling of bovine brain mixed gangliosides to agarose resulted in a matrix capable of reversibly binding MIF. GD1a-agarose was inactive in this respect.

Animals↗