Stimulation of [3H]thymidine uptake in mouse marrow by granulocyte-macrophage colony stimulating factor from mouse lung conditioned medium

Horak, Helena; Turner, A R; Shaw, Andrew; Yau, Oy-wah

doi:10.1016/0022-1759(83)90417-9

Cited by 31 publications

(8 citation statements)

References 8 publications

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“…epithelial cells secrete copious amounts of CSFs upon stimulation with bacterial lipopolysaccharide [39]. This is consistent with the fact that lungs from lipopolysaccharide-injected mice are a rich source of CSFs [40]. The number of lymphocytes was also reduced by IFN-y instillation, which is in keeping with the ability of IFN-y to prevent !ymphoproliferation [41].…”

Section: Discussionsupporting

confidence: 73%

Murine hypersensitivity pneumonitis: bidirectional role of interferon‐gamma

Michel

Ghadirian

1992

Clin Experimental Allergy

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C57BL/6 mice were instilled intranasally with optimal doses [150 micrograms of antigen 3 days a week) of the actinomycete Faeni rectivirgula to induce an experimental hypersensitivity pneumonitis. Some control mice received normal rat IgG as controls, whereas other mice received 1 mg weekly of rat anti-murine interferon gamma (IFN-gamma) antibody by the intraperitoneal route and 200 micrograms by the intranasal route given 2 days before and during the challenge period before each instillation. Control mice developed a clear hypersensitivity pneumonitis characterized by an early neutrophilic response at 3 days and a later influx of mononuclear cells (nine- to tenfold increase in cell number. P less than 0.001 vs saline instilled mice at 4 weeks post-treatment). F. rectivirgula instillation determined a sharp increase in the lung index (80% increase in lung weight, P less than 0.005 vs saline treated mice), as well as a significant fibrosis at 4 weeks (twofold increase in lung hydroxyproline levels). Cytokine measurements showed that tumour necrosis factor alpha (TNF alpha) was present in the broncho-alveolar lavage (BAL) of challenged mice at 4 weeks when the BAL was obtained 8 hr after the last challenge (130 U/ml). Treatment of mice with the monoclonal antibody against IFN-gamma was associated with very few changes in the number of cells in the BAL of challenged mice. The lung index of challenged mice was significantly reduced by infusion of the anti-IFN-gamma antibody. Anti-IFN-gamma treatment resulted in decreased levels of TNF alpha in the BAL of F. rectivirgula after 4 weeks of treatment (56 U/ml, P less than 0.01). Moreover, depletion of endogenous IFN-gamma in F. rectivirgula-instilled mice resulted in a diminished lung fibrotic response (P less than 0.01 vs mice treated with F. rectivirgula and control antibody). We also studied the effect of exogenous IFN-gamma adminstration on the development of lung disease. Groups of mice received recombinant gamma interferon (IFN-gamma) (1000 U) intraperitoneally just before the first treatment and also daily, whereas controls received saline or IFN-gamma alone (no F. rectivirgula challenge). After 4 weeks of treatment, mice were killed and various markers of the disease were evaluated. As mentioned before, bronchoalveolar lavage (BAL) cell number was increased tenfold in mice treated with F. rectivirgula, whereas mice given F. rectivirgula and IFN-gamma had only a threefold increase in BAL cell number, determined mostly by a decrease in alveolar macrophage recruitment in the lungs.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 73%

Murine hypersensitivity pneumonitis: bidirectional role of interferon‐gamma

Michel

Ghadirian

1992

Clin Experimental Allergy

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“…Test supernatants were added (10 tA) and the plates incubated at 37°C. BMPA was assayed by adding [SH]thymidine (see below) at 48 h and harvesting the cells at 64-66 h (13). After 5 or 6 d the number of eosinophils was estimated by assaying eosinophil peroxidase using O-phenylenediamine as hydrogen donor, and reading A492 in a Titertek Multiskan (Flow Laboratories Ltd., Irvine, Ayrshire, Scotland).…”

Section: Methodsmentioning

confidence: 99%

Identification of a lymphokine that stimulates eosinophil differentiation in vitro. Its relationship to interleukin 3, and functional properties of eosinophils produced in cultures.

Sanderson¹,

Warren²,

Strath³

1985

The Journal of Experimental Medicine

279

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Factors stimulating eosinophil differentiation in vitro have been studied by means of a liquid bone marrow culture system in which the number of eosinophils is estimated directly by morphology or indirectly by assay for eosinophil peroxidase. The results show that eosinophil colonies are not formed in agar, emphasizing the importance of the liquid culture system. Three types of evidence identify a novel lymphokine, eosinophil-differentiating factor (EDF). (a) Coordinate analysis of lymphokine activity in media conditioned by a panel of parasite antigen and another panel of alloantigen-reactive T cell clones indicates that EDF is distinct from interleukin 2 (IL-2), IL-3, and bone marrow proliferation activity (BMPA). (b) A T hybrid (NIMP-TH1) produces EDF but no IL-2, IL-3, interferon, or colony-stimulating factor. (c) Gel filtration of conditioned media (CM) indicates that NIMP-TH1 and a T clone (NIMP-T2) produce EDF (Mr 46,000). NIMP-T2 also produced IL-3 (Mr 26,000) but this was easily separated from EDF. IL-3 is also shown to have eosinophil differentiation activity (EDA) but this represents a very small proportion of the EDA in T2-CM. Fractionation of WEHI-3-CM indicates that EDA from this source has a similar elution profile to IL-3 (Mr 35-36,000). Furthermore, a comparison of the relative activities in purified IL-3 and WEHI-3-CM indicates that all the EDA can be attributed to the IL-3 in the latter. EDF is shown to stimulate production of eosinophils in long-term bone marrow cultures; the kinetics of eosinophil production suggests that EDF is acting on committed precursors in the bone marrow. The transient nature of eosinophil production suggests that precursors from multipotential stem cells are not produced. The eosinophils produced in these cultures are morphologically normal and functional in that they lysed sheep red blood cells coated with IgG1, IgG2a, and IgG2b, but not with IgM, IgA, or IgE. In addition, they were capable of adhering to and killing Schistosoma mansoni schistosomula.

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“…To investigate biologic activity of this mbGM-CSF, we evaluated whether the membrane-bound component was able to stimulate syngeneic bone marrow cells, cells which express the GM-CSF receptor and proliferate in the presence of soluble GM-CSF in a dose-dependent manner. 15 Cell membrane fractions isolated from each of the three types of B16.F10 tumor cells (wild type, mbGM-CSF, and secGM-CSF) were used in the bone marrow proliferation assay. We utilized membrane fractions from each of the three cell lines rather than intact cells to ensure that the GM-CSF activity measured was only from the mbGM-CSF that had been expressed as an integral membrane component.…”

Section: Mbgm-csf Retains Its Biologic Activity When Present As An Inmentioning

confidence: 99%

“…Biologic activity of the mbGM-CSF engineered on to the surface of B16.F10 cells was measured by a bone marrow proliferation assay described previously, 15,17 with a modification in sample preparation. Briefly, aliquots of the following cell lines containing 10 7 cells were harvested with cell dissociation buffer and pelleted: B16.F10, clone 2B10 (expressing mbGM-CSF) and clone sec20 (expressing secGM-CSF).…”

Section: Biologic Activity Of the Mbgm-csf Expressed On The B16f10 Cmentioning

confidence: 99%

Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine

et al. 2002

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Cancer vaccines composed of tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membranebound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on

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Stimulation of [3H]thymidine uptake in mouse marrow by granulocyte-macrophage colony stimulating factor from mouse lung conditioned medium

Cited by 31 publications

References 8 publications

Murine hypersensitivity pneumonitis: bidirectional role of interferon‐gamma

Murine hypersensitivity pneumonitis: bidirectional role of interferon‐gamma

Identification of a lymphokine that stimulates eosinophil differentiation in vitro. Its relationship to interleukin 3, and functional properties of eosinophils produced in cultures.

Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine

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