UMLS:C0153470 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0153470 (Spleen)
4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spleen cells from C57BL/6 mice bearing primary tumors induced by the Moloney strain of murine sarcoma virus (MuSV) strongly inhibited the uptake of tritiated thymidine (3H-TDR) by RBL-5 lymphoma cells in a 48-hour growth-inhibition assay (GIA). This activity was first detected 7 days after MuSV was injected; it peaked at 14 days, and was usually no longer detectable after 18-21 days. It could be detected at effector cell/target cell ratios between 20:1 and 5:1, at which normal spleen cells had a growth-promoting effect. The effector cells in the GIA were not T cells, and various depletion experiments suggested that they were macrophages. Macrophages of a purity of over 95% were obtained in the glass-adherent fraction of thioglycollate-induced peritoneal exudate cells (PEC). PEC were growth inhibitory when obtained from either normal or MuSV tumor-bearing mice. However, at effector cell/target ratios of 2.5:1, only PEC from MuSV tumor-bearing mice had an effect; PEC from normal mice were inactive. Activity of spleen cells in the GIA appeared distinct from T-cell-dependent specific cytotoxicity, which was not affected by removal of macrophages. Activity in the GIA was nonspecific, and target cells which do not cross-react with RBL-5 cells were equally inhibited. Furthermore, spleen cells from mice bearing primary tumors induced by 3-methylcholanthrene were also fully active against RBL-5 cells. Supernatants from spleen cell cultures obtained from mice 14 days post injection with MuSV also inhibited the incorporation of 3H-TDR by RBL-5 cells in vitro. However, this effect seemed to be an artifact, since the tumor cells proliferated equally well in the presence or absence of the supernatants. In contrast, the direct effect of spleen cells from MuSV tumor-bearing mice was reflected both by an inhibition of cell proliferation and by inhibition of 3H-TDR incorporation.
...
PMID:Inhibition of in vitro growth of lymphoma cells by macrophages from tumor-bearing mice. 17 34

In this study, we determined whether spleen cells from Listeria monocytogenes-immunized mice were cytolytic for Listeria-infected macrophages. Spleen cells freshly obtained from immunized donors were unable to lyse Listeria-infected macrophages unless they were first stimulated in vitro for 2-3 days with Concanavalin A (ConA) or L. monocytogenes. Spleen cells from non-immunized mice developed cytolytic activity after incubation with ConA, but not with L. monocytogenes. Cytolytic spleen cells demonstrated an equivalent ability to lyse uninfected and Listeria-infected thioglycollate elicited peritoneal macrophages. Maximal cytolysis required co-incubation of effector and target cells for 18-20 h. Spleen cell culture supernatants did not lyse macrophages, suggesting that cytolysis required direct contact. Preincubation of immune spleen cells with ConA decreased their ability to transfer anti-listeria resistance in the spleens, but not the livers of recipient mice. Depletion of CD4+ or CD8+ cells did not significantly reduce the ability of ConA-incubated Listeria-immune spleen cells to transfer resistance. Despite being cytolytic for Listeria-immune infected macrophages, ConA-stimulated non-immune spleen cells did not transfer anti-listeria resistance. These results indicate that cytolytic cells can be generated by short-term incubation of spleen cells with antigen or mitogen. The dissociation between in vitro cytolytic activity and ability to transfer protection, however, suggests that the two biological activities are not inextricably linked.
...
PMID:Dissociation of macrophage cytolysis and ability to transfer anti-listeria resistance by concanavalin A-stimulated spleen cells. 135 78

Flow cytometry (FC) and fluorescent in situ hybridization (FISH) were used to detect in vivo induced IL-1 alpha (a) messenger RNA. Spleen cells and thioglycollate-induced peritoneal exudate cells (PEC) were harvested from Balb/C mice three hours after intraperitoneal injection of 20 micrograms LPS. Cells from each population were phenotyped for MAC or IAd, fixed in 4% paraformaldehyde and then permeabilized with 70% ETOH. RNA-RNA FISH was performed by incubating suspended cells at 37 degrees C for 17 hours with biotinylated sense IL-1a, antisense IL-1a or antisense IL-2 probes in 50% formamide. Hybridized cells were washed in 2X SSC, treated with RNAse, stained with avidin conjugated to fluorescein (FITC) or allophycocyanin (APC) and analyzed immediately by FC. Initially, avidin-FITC was used to detect hybridized probe. Dual fluorescent FC analysis of IL-1a mRNA expression in LPS stimulated IAd+ cells showed an increase in mean fluorescent intensity (MFI) of 51 log channels (0.25 logs) when compared to unstimulated cells. Additionally, induction of specific IL-1a mRNA expression in cells from LPS treated animals was illustrated by increases in percent positive cells (24%) and in equivalent soluble fluorescein molecules (ESFM) bound (47%) when compared to cells from vehicle treated mice. Unhybridized cells and cells hybridized with control antisense IL-2 probe did not exhibit increases in MFI or ESFM. In subsequent experiments on MAC+ PEC, the use of avidin-APC to detect bound probe resulted in a greater separation between the FISH signals of antisense IL-1a and control sense probe (121 log channels, 0.6 logs) than that seen with FITC.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Detection of in vivo-induced IL-1 mRNA in murine cells by flow cytometry (FC) and fluorescent in situ hybridization (FISH). 157 48

Spleen cells from non-obese diabetic mice were found to generate low interleukin 2 production and cell proliferation in response to concanavalin A. However, some of non-obese diabetic mice maintained in the same environment preserved their responsiveness to this T cell mitogen. Non-obese diabetic mice at every age had a higher percentage of Thyl.2, L3T4, and Lyt2-positive spleen cells than did control mice, suggesting that the dysfunction of spleen cells did not depend on the number of T cells or the ratio of these subpopulations. Evidence for macrophage-mediated suppression participating in the deficient function of splenic lymphocytes in this mouse model of insulin-dependent diabetes includes: 1) the restoration of mitogen-induced interleukin 2 production after the macrophages have been depleted by silica absorption form spleen cells; 2) the complete suppression of the cell proliferation by thioglycollate-stimulated peritoneal exudate cells from non-obese diabetic and control mice, and the partial suppression by spleen macrophages from non-obese diabetic mice; 3) the reversal of the suppression of interleukin 2 production by the prostaglandin synthetase inhibitor indomethacin (0.1-1 microgram/ml); 4) the partial suppression of interleukin 2 production, conversely, by the exogenous prostaglandins E1 and E2 (2.5 x 10(-6) mol/l). These results indicate that the activated macrophages existing among the spleen cells suppress the response of splenic T cells to concanavalin A. This impairment may contribute to the pathogenesis of insulin-dependent diabetes in non-obese diabetic mice.
...
PMID:Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mouse. 278 66

A new class of synthetic biological response modifiers (BRMs) has been produced by combining a highly electrophilic reactant, 2-methyl-2, 5-dihydrofuran (a cyclic acetal of cis-3-acetyl acrolein), with L-ascorbic acid. The parent class of compounds can be referred to as methylfurylbutyrolactones (MFBL), previously termed Nafocare B. This parent molecule is amorphous, has a molecular weight of 252.7, and the chemical name [3,6] cyclohemiketal of 2-(5-methyl-2-furyl)-3-keto-L-butyrolactone. Two crystalline forms were produced by a reaction of the MFBL parent molecule with either succinic anhydride or succinimide, to create MFBL-SA (Nafocare B2) and MFBL-S (Nafocare B3) dimers, respectively. The structure of these compounds has been confirmed by modern methods of analytical chemistry, including x-ray crystallography. All three forms of the MFBLs showed negligible toxicity in single-dose acute LD-50s in mice. Also, the MFBLs did not demonstrate genotoxic activity at 800 mg/kg in the mouse micronucleus assay. The MFBLs are immunostimulatory in assays involving T- and B-lymphocytes, but not in immunoassays on macrophages derived from resident- or thioglycollate-elicited peritoneal exudate cells (PEC). Spleen cells from mice treated 4 days via the intraperitoneal, intravenous, or the oral routes responded significantly over controls to suboptimal stimulatory concentrations of polyclonal mitogens in the lymphocyte stimulation assay. The MFBLs were not mitogenic, since they did not increase DNA synthesis in resting spleen cells from MFBL-treated mice. Antibody production is also amplified by the MFBLs. Mice immunized with sheep erythrocytes, a T-cell-dependent antigen, and treated with MFBLs had a 200-800% increase in the numbers of antibody-producing splenic lymphocytes detected by the Jerne hemolytic plaque assay. Also, mice immunized with soluble bovine serum albumin (BSA), and treated with a MFBL, demonstrated at least a fourfold increase in IgG-specific antibodies to BSA, when compared with controls. To demonstrate effects of MFBLs on macrophages, we used the Fc receptor (FcR) surface marker and superoxide anion assays. Only at the highest in vitro dose of MFBL (16 micrograms/ml) was a significant increase in erythrocyte antibody rosette formation detected, using resident macrophages isolated from PEC. In the superoxide anion release assay neither resident- nor thioglycollate-elicited PECs, obtained from in vivo-treated mice or macrophages treated in vitro, showed increased production of superoxide anion.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:A new class of synthetic biological response modifiers: the methylfurylbutyrolactones (Nafocare B). 302 12

Prior work has shown that purified, resident, and inflammatory peritoneal macrophages are weak stimulators of the allogeneic MLR. We have identified conditions whereby thioglycollate-elicited macrophages become stimulatory, but primarily for the CD8+ T cell subset. The conditions were to treat the macrophages with neuraminidase and to supplement the MLR with rIL-2. These treatments together led to proliferative and cytotoxic responses by isolated CD8+ but not CD4+ T cells. Likewise when MHC-congenic strains were evaluated, an MLR was observed across isolated class I but not class II MHC barriers. Pretreatment of the macrophages with IFN-gamma further enhanced expression of class I MHC products and stimulatory activity, but did not seem essential. While these treatments did not render macrophages stimulatory for an MLR in purified CD4+ cells, blastogenesis of CD4+ cells was observed when the MLR involved bulk T cells. Small allogeneic B lymphocytes behaved similarly to macrophages, in the pretreatment with neuraminidase and supplementation with rIL-2 rendered B cells stimulatory for allogeneic, enriched, CD8+, but not CD4+, T cells. Spleen adherent cells, which are mixtures of macrophages and dendritic cells, stimulated both CD4+ and CD8+ T cells, and neither neuraminidase nor exogenous IL-2 was required. We think that these data suggest that most macrophages and small B cells lack three important functions of dendritic cells: a T cell-binding function that can be remedied by neuraminidase treatment, a T cell growth factor-inducing function that can be bypassed with exogenous IL-2, and an IL-2 responsiveness function that is required by CD4+ lymphocytes.
...
PMID:Neuraminidase-treated macrophages stimulate allogenic CD8+ T cells in the presence of exogenous interleukin 2. 326 11

Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12-week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population.
...
PMID:Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection. 624 28

Spleen cells from scid mice produce high levels of IFN-gamma when exposed to either live tachyzoites of Toxoplasma gondii or a soluble parasite extract. Small numbers of parasites are sufficient to stimulate this response, which is also induced by cell-free supernatants of cultured tachyzoites. The parasite molecules responsible for triggering IFN-gamma production are heat-labile but resistant to freezing and thawing. Depletion of NK cells or adherent cells from the splenocyte population abolishes the response. Moreover, cultured bone marrow-derived NK cells are stimulated by Toxoplasma to produce IFN-gamma, but only when supplemented with adherent peritoneal washout or thioglycollate-induced exudate cells. Supernatants of macrophages preincubated with T. gondii extract also induce IFN-gamma synthesis by cultured NK cells. Addition of neutralizing mAb against TNF-alpha abolishes the IFN-gamma response of scid spleen cells exposed to the parasite or of NK cells incubated with supernatants of adherent cells stimulated with T. gondii extract. Moreover, splenic adherent cells produce low levels of TNF-alpha in response to the parasite. Nevertheless, TNF-alpha alone is not sufficient to trigger IFN-gamma production from purified NK cell populations. These findings provide the first example of the stimulation of T-independent IFN-gamma production by a protozoan. The ability of T. gondii to trigger this pathway may underlie its induction of strong IFN-gamma-dependent nonspecific and specific cell-mediated immunity.
...
PMID:Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha. 847 45

Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through Fc-dependent, but C-independent pathways during anti-CD20 immunotherapy.
...
PMID:The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice. 1577 4

Diacetylpolyamines (DAPs) are novel, promising tumor related markers, but the mechanism sustaining their good sensitivity and specificity is not known. This investigation was conducted on the production mechanism of DAPs, using (C57BL/6NxDBA/2N)F(1) mice and the P388D(1) (lymphoid) tumor system. Spleen adherent cells from mice injected with thioglycollate produced N(1),N(12)-diacetylspermine (DAM) in co-culture with P388D(1) cells. Macrophages among peritoneal exuded cells also produced DAM actively, while granulocytes, another innate immune cell, did not. The participation of macrophages in vivo was confirmed by depletion experiments using dichloromethylene diphosphonate liposomes. The supply of exogenous spermine and a deficiency of glucose, which tend to occur with tumorigenesis, resulted in an explosion of the production of DAM by macrophages. The number of macrophages required for the elevation of DAM for a diagnosis in humans was estimated at less than 4.2 x 10(8). The mechanism and productivity studied in this work support the superiority of DAM as a tumor related marker. Diacetylation may relate to the depression of macrophage function by spermine.
...
PMID:Host macrophages produce diacetylspermine related with tumorigenesis. 1645 92

1