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Results for “Macrophage suppression”

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At least 19 recordsLinked to original sources

PubMed1991

Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.

Tumors are known to produce factors suppressing macrophage function. In this study we demonstrated in vitro suppression of macrophage chemiluminescent oxidative burst associated with viable cells and cell-free extracts of two urological neoplasms--murine renal cell carcinoma (Renca) and murine bladder tumor (MBT). Suppression was reversed by extracts of two Chinese medicinal herbs, Astragalus membranaceus (AM) and Ligustrum lucidum (LL). Murine macrophage cell line J774 was incubated with either the viable tumor cells or the cell-free tumor extract for 18 hours at 37C and 5% CO2. Chemiluminescent oxidative burst as an indicator of macrophage function was triggered by adding zymosan A suspension containing luminol and assayed in an automated luminometer. Photon emission over time was counted and the results were expressed as integrated photon emission. Significant dose-related depression of oxidative burst occurred with either the viable tumor cells or the cell-free tumor extracts. Depression was partially or completely reversed by the presence of 50-100 micrograms./ml. of either the AM or the LL extract. AM and LL have previously been shown to modulate immune response. Data from this study suggest that they may also exert their antitumor activity via abolition of tumor-associated macrophage suppression.

Animals↗

PubMed1992

Myelinated fiber regeneration after sciatic nerve crush: morphometric observations in young adult and aging mice and the effects of macrophage suppression and conditioning lesions.

To study myelinated nerve fiber regeneration during aging, the right sciatic nerves of 6- and 24-month-old mice were crushed at the sciatic notch. Two, 4, and 8 weeks later, both groups of mice were perfused. The sciatic nerves were processed so that the transverse sections of each nerve subsequently studied by light and electron microscopy included the entire posterior tibial fascicle 5 mm distal to the crush site. Two weeks after axotomy, fascicles of aging mice contained significantly fewer regenerated myelinated fibers than those of young adults. After 4 weeks, the difference in the number of myelinated fibers was less. However, measurements of myelinated fibers in fascicles of aging mice showed that areas of Schwann cell cytoplasm and myelin were significantly reduced at all intervals. In contrast, although axon diameters in aging mice were somewhat less 2 weeks after crushing, the difference decreased with time, suggesting that in nerves of aging mice, regenerative responses of Schwann cells were more affected than those of axons. Other experiments in young mice showed that myelinated fiber regeneration could be retarded by suppressing macrophage responses and was not significantly changed by conditioning lesions before crush injury.

Adaptation, Physiological↗

PubMed2026

Quantum computing-assisted validation of a conserved macrophage suppression module shared by ASFV and PEDV.

BACKGROUND: African swine fever virus (ASFV) and porcine epidemic diarrhea virus (PEDV) differ in viral biology and cellular tropism, yet both pathogens suppress macrophage-mediated immune responses in pigs. OBJECTIVE: To identify a conserved macrophage suppression module shared by ASFV and PEDV and evaluate quantum computing as an independent framework for biological network validation. METHODS: Integrated analysis of publicly available GEO datasets (GSE231435 for ASFV and GSE306895) identified 471 shared downregulated genes. A network- and multi-omics-informed 20-gene core was selected and encoded as a 20-qubit modularity-based Quadratic Unconstrained Binary Optimization (QUBO) problem. Community detection was benchmarked using the Quantum Approximate Optimization Algorithm (QAOA) on both the IBM Quantum Aer simulator and the 156-qubit IBM Fez (Heron r2) quantum processor and compared with brute-force enumeration and simulated annealing. RESULTS: A conserved macrophage suppression module shared by ASFV and PEDV was identified. For the STRING protein-protein interaction network, QAOA at circuit depth p = 3 reproduced the brute-force optimum with an approximation ratio of 1.000. In contrast, performance progressively declined in the denser co-expression network with increasing circuit depth, consistent with noise accumulation under current Noisy Intermediate-Scale Quantum (NISQ) conditions. Multi-run consensus analysis identified stable hub genes, including MMP9 and SLA-DOA, as well as genes exhibiting variable community assignments. CONCLUSION: These findings reveal a conserved macrophage suppression module shared between ASFV and PEDV and demonstrate that quantum computing can serve as an independent validation framework for biologically meaningful host-response networks. Network topology emerged as a key determinant of QAOA performance on real NISQ hardware.

Animals↗

PubMed1982

Tumor-promoting diterpene esters prevent macrophage activation and suppress macrophage tumoricidal capacity.

The efficacy of varied diterpene ester type tumor promoters in suppressing the acquisition as well as the manifestation of cytolytic activity by macrophages was investigated. These mechanisms, believed to be basic to natural antitumor resistance, were markedly suppressed not only by the phorbol ester, TPA, but also by several other tumor promoters of the polyfunctional diterpene ester type covering tigliane, ingenane, and daphnane derivatives. The promoters were particularly effective in preventing the lymphokine-induced enhancement of natural cytolytic activity in resting macrophages. Moreover, the same promoters suppressed the manifestation of cytotoxicity by previously activated macrophages. Their influence on the effector phase was less pronounced than on the activation phase. In sharp contrast, typical solitary carcinogens of the polycyclic aromatic hydrocarbon type exerted little or no activity in the macrophage test systems. Since TPA had already been shown to suppress the natural killer activity in vitro and to abrogate host tumor resistance in vivo, the present findings lend further support to the interpretation that tumor promoters, apart from directly stimulating the outgrowth of transformed cells, may function via interference with natural antitumor effector systems.

Animals↗

PubMed1995

Recombinant human granulocyte colony-stimulating factor treatment improves macrophage suppression of granulocyte and macrophage growth after burn and burn wound infection.

Granulocyte and macrophage production after burn injury or burn wound infection is significantly reduced and further compromised by endotoxin (ET). Moreover, the macrophage seems to be the major source of this bone marrow suppression. We sought to determine if recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that is capable of improving survival after experimental burn wound sepsis, altered postburn macrophage-mediated marrow suppression. Groups of male BDF1 mice (n = 6 to 10) receiving a 15% total body surface area burn +/- infection (B or B + I) with Pseudomonas aeruginosa were injected with 100 ng rhG-CSF twice daily. On day 3, peritoneal-elicited macrophages (5 x 10(6) cells/mL) from either rhG-CSF-treated or control (5% dextrose in water) mice were incubated +/- ET (300 ng/mL). The resultant macrophage supernatant was added to cultures of target marrow granulocyte-macrophage progenitor cells (GM-CFC) at a volume of 1:10. The GM-CFC growth as a percentage of cultures not containing macrophage supernatant were compared and reductions in the number of GM-CFC taken as an index of marrow suppression. Macrophages obtained from B and B + I animals reduced target GM-CFC growth, compared with macrophages from normal animals (B vs. normal animals p < 0.05). In addition, ET-stimulated macrophages induced further bone marrow suppression for all three groups (p < 0.01). Macrophages from granulocyte colony-stimulating factor-treated animals caused significantly less bone marrow suppression, compared with untreated animals for all groups (p < 0.05 to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Macrophage suppression of granulocyte and macrophage growth following burn wound infection.

Burn injury results in alterations in granulocyte and macrophage production. Since macrophages may mediate these alterations we determined the effects of macrophages obtained from animals with burn injury with and without infection on the growth of marrow granulocyte macrophage progenitor cells (GM-CFCs). The in vitro GM-CFC growth response for maximally stimulated cultures was reduced by 25% to 30% (p < 0.01) for burned and infected (B + I) animal macrophages compared with burned (B) or sham (S) animals. Macrophages stimulated with endotoxin caused a further reduction for all groups in GM-CFC growth, most notably so for B + I macrophages. Burned + infected animal macrophages or all-endotoxin macrophages cocultured with indomethacin did not suppress GM-CFC growth. Following burn injury and infection, macrophages spontaneously elaborate negative regulators of myeloid growth that is further increased by endotoxin. It is likely that PGE2, a known negative regulator of granulocyte macrophage growth, is largely responsible for this suppressive effect.

Animals↗

PubMed1987

Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products.

In the present study, we examined the modulation of MHC class II and class I gene products on BALB/c macrophages infected with the obligate intracellular protozoan Leishmania donovani. Our findings indicated that this organism suppressed macrophage expression of both classes of MHC antigens. These effects varied somewhat, depending on whether cells were in the basal state or were stimulated with interferon-gamma. Thus, class II density on interferon-gamma-treated infected macrophages was suppressed by as much as 90%, relative to lymphokine-stimulated control cells. Induction of H-2K and H-2D by lymphokine treatment of infected macrophages was also markedly reduced. In the basal (non-lymphokine-treated) state, infected cells also showed reduced expression of H-2K and H-2D, but not I-A or I-E. The latter result was related to minimal levels of class II molecules on normal, in vitro cultured macrophages. Suppression of MHC gene products correlated with both the duration and intensity of leishmania infection and could not be overcome by increasing doses of interferon-gamma. Culture of cells under conditions of cyclooxygenase inhibition completely abolished elevated synthesis of prostaglandin E2 by infected macrophages and augmented their responsiveness to lymphokine induction of class II antigens by 60 to 80%. These results indicate that L. donovani is capable of subverting a critical macrophage accessory function required for the induction of T lymphocyte immunity. This mechanism could account, at least in part, for defective parasite-specific cell-mediated immunity seen during infections with this protozoan.

Animals↗

PubMed1990

Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis.

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.

Alprostadil↗

PubMed2005

Selective macrophage suppression during sepsis.

Polymicrobial sepsis induces suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. We examined whether macrophages were refractory to only LPS challenge or if they were immunoparalyzed and unable to respond to other stimuli such as lipoteichoic acid (LTA) or zymosan (ZYM). This study evaluated the capacity of peritoneal macrophages to produce pro-inflammatory and anti-inflammatory cytokines as well as chemokines following mild or severe sepsis induced by cecal ligation and puncture (CLP). Peritoneal macrophages were isolated 29 h after CLP and challenged with different stimuli. LPS was a more potent stimulus for cytokine induction than LTA or ZYM in both mild and severe sepsis. In mild sepsis, the macrophage cytokine response to LPS was selective and less refractory than in severe sepsis. While production of IL-6 and KC was reduced, secretion of TNF-alpha and MIP-1alpha was enhanced in those cells isolated from mice with mild sepsis. Production of IL-10 and the IL-1 receptor antagonist , MIP-2, and MCP-1 in response to LPS stimulation was equivalent to the amount produced by naive macrophages. Our results indicate that macrophages are not immunoparalyzed during sepsis and may still be induced to secrete some inflammatory mediators.

Animals↗

PubMed1998

Effect of macrophage suppression with silica on the proliferation of Schwann cells during Wallerian degeneration.

Effects of macrophage suppression on Schwann cell proliferation in Wallerian degeneration was investigated in vitro with thymidine autoradiography. Sciatic nerves of C57BL mice were transected shortly after an intraperitoneal injection of silica dust and Schwann cells were harvested at 1, 2, 3, 5, 7, and 10 days post-transection. In silica treated mice, Schwann cells from post-transected nerve stumps proliferated despite marked suppression of macrophages, although there was some initial delay. The results of this study suggest that the mechanism of Schwann cell proliferation is multifactorial and in addition to the influence of growth factors mediated and released by macrophages, other factor(s) such as degenerated axolemma may play a more pivotal role in Schwann cell proliferation in vivo.

Animals↗

PubMed1997

C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

Cells, Cultured↗

PubMed1989

The role of suppressive macrophages in influenza virus-induced immunosuppression.

To confirm the role of macrophages in influenza virus (IV)-induced immunosuppression (IS) of mice, silica, a selectively destructive agent for macrophages, was tested for its ability to influence the IV-induced IS. Silica completely abolished that effect. In contrast, Indomethacin--a prostaglandin inhibitor--did not influence the IV-induced IS. Peritoneal macrophages of mice infected with IV were suppressive for plaque forming cell (PFC) response of normal spleen cells in vitro. The assumption was made that suppressive macrophages were induced by IV in mice. However, no suppressive factors were found in the culture fluid of these cells.

Animals↗

PubMed2006

B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.

Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.

Animals↗

PubMed1983

Inhibitory factors derived from human tumors: isolation of factors which suppress macrophage mediated cytotoxicity.

Previously, we had demonstrated that plasma inhibitory factors obtained from colon cancer patients suppressed macrophage mediated cytotoxicity. When this inhibitor was further purified, four fractions (A, B, C and D) with inhibitory activity were isolated. In this study, it was found that these four purified inhibitory factors also dramatically decreased the extent of macrophage mediated cytotoxicity induced by LPS when added during the activation phase of the assay. When the secretions from a variety of fresh tumors as well as several established tumor cell lines were purified utilizing immunoadsorbent techniques, those same inhibitory factors were recovered. It was found that 8 of the 11 secretions obtained from a variety of fresh tumors and established tumor cell lines secreted inhibitor A; 6 secreted inhibitor B and 5 secreted inhibitor C. (The presence of inhibitor D was not studied.) Furthermore, one of the 11 tumors studied secreted none of these inhibitory factors. These findings lend support to the theory that these inhibitory factors which are initially produced by the tumor and subsequently shed into the sera ultimately lead to in vivo suppression of macrophage mediated cytotoxicity.

Ascitic Fluid↗

PubMed1995

Macrophage colony stimulatory factor-activated bone marrow macrophages suppress lymphocytic responses through phagocytosis: a tentative in vitro model of Rosai-Dorfman disease.

NBXFO hybridoma cells produced macrophage colony-stimulating factor (M-CSF), which stimulated the growth of murine bone marrow-derived macrophages with potent suppressor activity. These macrophages suppressed lymphocyte responses to mitogens and antigens in a dose-dependent manner. Using a transwell chamber, we demonstrated that macrophages needed physical contact with the lymphocytes to suppress lymphocyte proliferation on day 1 in the concanavalin A mitogen reaction. In addition, no soluble suppressor factor was detected at that time. The number of lymphocytes disappeared with time when they were cocultured with the macrophages. Electron microscopy revealed that the macrophage phagocytosized the lymphocytes after 7 1/2 h. Dextran sulfate, heparan, and fucoidan prevented the macrophages from suppressing the lymphocytes. This phenomenon resembles the human disease sinus histiocytosis, also called Rosai-Dorfman disease, in which macrophages (histiocytes) phagocytosize autologous lymphocytes; occasionally, this disease is associated with immunological abnormalities. Thus we believed that macrophage-activating cytokines, such as M-CSF, may stimulate macrophages to phagocytose lymphocytes in vivo.

Animals↗

PubMed1999

Induction of apoptosis in activated T cell blasts by suppressive macrophages: a possible immunotherapeutic approach for treatment of autoimmune disease.

Large suppressive macrophages (LSM) were induced by restimulating spleen cells from rats with experimental autoimmune myasthenia gravis (EAMG) in vitro, with the autoantigen acetylcholine receptor (AChR) in the presence of cyclosporine A. LSM, purified from these cultures, are extremely potent suppressors of AChR-stimulated lymphoproliferative responses and antibody responses in vitro. In the present study, we have analyzed the factors that determine susceptibility of primed lymph node cells (pLNC) to suppression by LSM and examined the fate of these cells. We found three characteristics of pLNC that influenced their susceptibility to suppression. First, pLNC were required to be activated (by antigen in these experiments) in order for suppression to occur. Resting lymphocytes were not affected, even when they were present in cultures where antigen-activated lymphoblasts were being actively suppressed. Second, antigen specificity of the responder cells influenced their susceptibility to suppression by LSM. AChR-specific cells were relatively more susceptible to suppression by AChR-induced LSM than pLNC primed to an unrelated antigen, keyhole limpet hemocyanin. Third, T cell proliferation was suppressed by LSM to a far greater extent than antibody production by B cells. Using enriched T cell blasts generated from AChR-stimulated T cell lines, we found that LSM rapidly suppressed [3H]TdR uptake and induced DNA fragmentation assessed by the TUNEL assay (within 8 h of coculture) and induced morphological signs of apoptosis of T cells (within 24 h). Few, if any, blasts remained by 48 h of coculture. The ability to suppress an activated immune response permanently, without affecting nonactivated, bystander lymphocytes, holds promise that LSM, or their cellular products, could be used for immunotherapy of autoimmune diseases such as myasthenia gravis.

Animals↗

PubMed2007

Carbon dioxide suppresses macrophage superoxide anion production independent of extracellular pH and mitochondrial activity.

BACKGROUND: Superoxide anions released by activated macrophages during surgery are considered to be responsible for local cellular damage. Application of CO2 pneumoperitoneum during laparoscopy affects superoxide anion release, but the underlying mechanism remains unclear and the data reported are conflicting. We investigated the direct and pH-mediated impact of CO2 and air on macrophage superoxide anion production. METHODS: Cells of the NR 8383 rat macrophage cell line were incubated for 2 hours in 5% CO2, 100% CO2, and room air or pH 7.4, pH 6.5, and pH 5.5. The extracellular pH was monitored during incubation. At 0, 2, and 6 hours after incubation, the release of superoxide anions was determined fluorometrically. The mitochondrial activity was determined via the conversion of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] during and after incubation. RESULTS: Extracellular pH decreased to 6.4 during incubation in a CO2 atmosphere. The release of superoxide anions was significantly reduced immediately after CO2 incubation. It was restored at all other time-points. Decreasing the extracellular pH to 6.5 had no effect on superoxide anion release, whereas acidification of the extracellular milieu to pH 5.5 significantly suppressed subsequent superoxide release. Mitochondrial activity was significantly decreased by CO2 up to 2 hours and by acidic milieu up to 6 hours. Incubation in room air had no effect. CONCLUSIONS: Incubation in CO2 can directly suppress macrophage superoxide anion production. This effect is of short duration, fully reversible, and not correlated to changes in extracellular pH or mitochondrial activity. Air contamination does not affect macrophage superoxide anion release. We speculate that CO2 pneumoperitoneum could attenuate the intraoperative free radical production by directly inhibiting superoxide anion release of macrophages without long-lasting suppression of macrophages and their capacity to release superoxide anions postoperatively.

Air↗

PubMed1986

Macrophage suppression by a low-molecular-weight fraction of murine spleen cell culture supernatant.

Macrophage suppression has been reported to be mediated by a component of murine serum. The present investigation involves in vitro production of this macrophage modulator (suppressor) by concanavalin A-stimulated murine spleen cells. Spleen cell culture supernatant containing this suppressor, which has been called macrophage suppressor factor (MSF), caused a significant decrease in in vitro phagocytosis of Listeria monocytogenes by resident murine peritoneal macrophages. The molecular weight of MSF was determined by ultrafiltration to be less than 10,000, and the suppressor activity of MSF was not altered by heating at 100 degrees C for 30 min or storage at -70 degrees C for 6 months. MSF is resistant to treatment with Pronase E, but is, however, sensitive to acid hydrolysis. Activity of MSF in spleen cell culture supernatants from normal mice does not differ from that in supernatants from mice immunized with L. monocytogenes. It was determined that MSF is not affected by antigenic stimulation and is apparently produced constitutively.

Acids↗