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Query: UNIPROT:P06889 (Mol)
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C57BL/6 mice were given intranasal instillation of optimal doses of the actinomycete Faeni rectivirgula 150 micrograms/mouse 3 days/wk), an important offending agent causing hypersensitivity pneumonitis. This instillation was associated with a very significant increase in the lung weight of the mice and also a large increase (10-fold) in the number of cells recovered from the bronchoalveolar lavage (BAL) of instilled mice. Also, this instillation was associated with a very significant fibrosis at 4 and 8 wk (2-fold increase in hydroxyproline levels in the lungs). We determined the effect of depleting certain T-cell subsets on the progression of this inflammatory disease. Elimination of the L3T4 subset did not significantly affect the increase in the lung index, the lung cellular influx, or its profile. Fibrosis was also unaffected by this depletion of L3T4+ cells. Similarly, depletion of Lyt2+ (CD8+) cells did not lead to significant changes in these disease parameters. Depletion of all T cells (Thyl+) was also ineffective at modifying the number of infiltrating cells and the lung index score. However, identification of cell types in BAL showed that mice depleted of Thyl+ cells had a cellular influx that was almost exclusively neutrophilic throughout the instillation period, whereas control mice developed only a transient neutrophilic response to F. rectivirgula instillation, which was replaced by a recruitment of mononuclear cells, mostly macrophages. Also, depletion of Thyl+ cells before and during F. rectivirgula challenge had no effect on tumor necrosis factor-alpha levels in the BAL of treated mice (63 +/- 13 U/ml in anti-Thy1. 2 antibodies treated versus 52 +/- 10 U/ml in the BAL of control mice given F. rectivirgula).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Feb
PMID:T cells in hypersensitivity pneumonitis: effects of in vivo depletion of T cells in a mouse model. 154 Mar 81

Radiation leukemia virus (RadLV)-induced thymomas and malignant thymocytes from AKR mice have been shown to bind specifically retrovirus produced by these cell lines. Each lymphoma has been shown to have greatest specificity for cognate virus suggestive of an immune-specific receptor. The question of receptor identity has been addressed here using the RadLV-induced murine T cell lymphoma, C6VL/1, and antibodies specific for known cell surface determinants present on these cells. This lymphoma has been shown to bind both homologous and heterologous RadLV isolates, but to have greatest specificity for homologous retrovirus since homologous free virions can best block the interaction between cells and virus adhered to the wells of a microtitre plate. A clonotypic anti-TCR antibody has been shown to completely inhibit C6VL/1 binding to the homologous virus, RadLV/C6VL, but not to the heterologous virus, RadLV/VL3. Anti-CD4, anti-Thy1.2 as well as anti-H-2Kb and not anti-H-2Db antibodies were found to partially inhibit the interaction with both RadLV/C6VL and RadLV/VL3, yet neither of these virus preparations appears to be contaminated with Class I molecules as measured by radioimmunoassay. The binding interaction between C6VL/1 and RadLV/C6VL appears specifically to involve the TCR since antibody against the clonotypic site on the TCR heterodimer uniquely inhibits this interaction, while the binding of C6VL/1 to RadLV/VL3 appears to involve the H-2Kb molecule. When free virus particles were absorbed to receptors on C6VL/1, both RadLV/VL3 and RadLV/C6VL inhibited the binding of antibody to the TCR and CD4 molecules, while the binding of several anti-H-2Kb antibodies was specifically inhibited by RadLV/VL3. There are at least two known T cell surface structures involved in the interaction of the T cell lymphoma, C6VL/1, with RadLV. These are the TCR complex (comprising the TCR heterodimer and CD4), and the Class I H-2Kb molecule. Since the TCR molecule has been shown to comodulate with H-2Kb molecules when cells were cultured in the presence of anti-H-2Kb antibodies, and the CD4 and H-2Kb molecules have been shown to comodulate with the TCR on only a subpopulation of C6VL/1 cells treated with anti-TCR antibody, this suggests that the H-2Kb molecule may also be part of the larger molecular complex including CD4/8 which can form around the TCR heterodimer.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1989
PMID:Binding of radiation leukemia viruses to a thymic lymphoma involves some class I molecules on the T cell as well as the T cell receptor complex. 255 69

Immunotoxins were prepared by conjugating saporin, a ribosome-inactivating protein from Saponaria officinalis, to a monoclonal antibody against the Thy1.1 antigen, or to its F(ab')2 fragment. The immunotoxins were eight- to 16-fold more toxic to mice than free saporin. Injection of the immunotoxins induced necrosis of the liver and spleen, whereas free saporin caused necrosis of the epithelium of the kidney tubules. The cytoplasm of the hepatic parenchymal cells was affected by the immunotoxins, lesions being apparent in the rough endoplasmic reticulum and, later, in the mitochondria. These changes were associated with a reduced capacity to synthesise proteins both in the intact liver and by isolated liver microsomes. Studies of the in vivo distribution showed that 90% of the free saporin was removed from the bloodstream, mainly by the kidneys, within 10 min of injection. By contrast, the immunotoxins persisted in the blood for several hours and the only organ in which they consistently accumulated was the liver. The hepatotoxic effect of the immunotoxins was not due to their binding to liver cells via the antigen-binding sites or the Fc-piece of the antibody moiety, nor was it due to hepatic recognition of carbohydrate in the immunotoxin. It is concluded that free saporin, although capable of entering liver cells, is filtered so rapidly by the kidney that liver damage does not occur to a significant extent. Filtered saporin, however, is reabsorbed by renal tubules, whose epithelial cells are damaged. The antibody-saporin conjugate is too large to filter at the glomerulus and so has greater opportunity to penetrate into and to damage the hepatic parenchymal cell.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Hepatotoxicity of immunotoxins made with saporin, a ribosome-inactivating protein from Saponaria officinalis. 288 89

Polyclonal IgM PFC responses of unstimulated B cells induced by a B cell differentiation factor, B151-TRF2, have been shown to involve an Ia-dependent process which is inhibitable by anti-Ia monoclonal antibody (mAb). Moreover, we have demonstrated that when T cell-depleted (B10 x B10.BR)F1 (H-2b/k) spleen cells are fractionated based on their ability to bind to a B10 (H-2b) monolayer, the B151-TRF2 responses of the adherent and nonadherent cell fractions are markedly inhibited by anti-I-Ab and anti-I-Ak mAbs, respectively. From these results, we hypothesized that B cell-recognition of self-I-A products expressed on B cells is involved in the B151-TRF2-induced polyclonal B cell activation. The present study examined the genetic and cellular requirements for the successful separation of F1 B cells with parental monolayers in order to prove recognition by B cells of self-I-A products expressed on B cells. The experiments utilizing monolayers from H-2 congenic strains revealed that identity at the I-A subregion of the H-2 complex between responding F1 B cells and monolayer cells was necessary and sufficient for the successful separation of F1 B cells. In support of this conclusion, purified B cells and B cell lines expressing only parental I-A products on the surface could function effectively as monolayers. Masking of I-A determinants expressed on the monolayer with anti-I-A mAb almost completely abolished the successful separation of F1 B cells, whereas pretreatment of Ia antigens on responding F1 B cells with anti-Ia mAbs did not affect the subsequent separation, indicating involvement of receptor-I-A product interaction rather than like-like interaction in the separation of F1 B cells by the monolayer. The B151-TRF2 responses of purified B cells obtained from athymic nude mice were specifically inhibited by the relevant anti-I-A mAb but not by anti-L3T4 and anti-LFA-1 mAbs, both of which were inhibitory to the Ia-restricted T cell responses. In addition, anti-Thy1.2 mAb plus complement-treated spleen cells from athymic F1 nude mice were successfully fractionated with parental monolayer into two separate populations with restriction specificity for only one of parental I-A products. These results negate the involvement of Ia-restricted T cells in the Ia-dependent process of the B cell activation. Finally, it was demonstrated that there was no apparent difference in the expression of respective parental I-A products between F1 B cell subpopulations adherent and nonadherent to parental monolayers.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1987
PMID:Polyclonal B-cell activation by a B-cell differentiation factor B151-TRF2. IV. B151-TRF2-responsive F1 B cells consist of two separate populations capable of recognizing only one of the parental I-A products expressed on B cells. 350 23

HSV-1 amplicon vectors were used to express either a cytoplasmic (beta-galactosidase) or a membrane targeted protein (TIMP-Thy1) in primary neuronal cultures, and a human astrocytoma cell line. Whereas some cells became infected by vector particles alone others were simultaneously infected by both vector and helper particles. Our results show that IEHCMV and HSV-1 IE3 promoters are able to direct transgene expression in these cells in the absence of synthesis of helper virus transacting proteins, and stress the need of monitoring expression from both partners of an amplicon population, in order to differentiate transgene expression in cells singly infected with amplicon particles, from those infected by both amplicon and helper particles.
Brain Res Mol Brain Res 1995 May
PMID:Simultaneous detection of amplicon and HSV-1 helper encoded proteins reveals that neurons and astrocytoma cells do express amplicon-borne transgenes in the absence of synthesis of virus immediate early proteins. 760 39

Inhalation of elevated levels of ozone produces a potent inflammatory response in the lung. The magnitude of this response to ozone exposure in mice is inbred strain dependent with the susceptible phenotype being exemplified by the C57BL/6J (B6) strain and the resistant phenotype by the C3H/HeJ (C3) strain. To examine the role of T lymphocytes in the regulation of ozone-induced pulmonary inflammation, mice were pretreated by an intraperitoneal injection of anti-Thy1.2 monoclonal antibody (mAb), anti-CD4+ mAb, or isotype-matched control antibodies (0.5 mg each) and subsequently exposed for 72 h to either filtered air or ozone (0.3 ppm). Immediately after ozone exposure, the cellular profile in the bronchoalveolar lavage fluids (BALF) was assessed. In isotype-treated controls of both strains of mice, ozone exposure induced significant increases in the numbers of macrophages, neutrophils, lymphocytes, and epithelial cells recovered in the BALF; however, the magnitude of each cell type recovered was significantly greater in B6 mice as compared with C3 mice. Both anti-Thy1.2 and anti-CD4+ monoclonal antibody treatments decreased the number of each cell type recovered in the B6 mice and increased the number of cells in the C3 mice. To determine if the CD4+ T-cell-derived cytokine interleukin (IL)-4 was involved in the differential effect of T-cell depletion on the ozone-induced inflammatory responses of C3 and B6 mice, mice were pretreated with either 400 ng of recombinant mouse IL-4 or vehicle, or 5.0 mg anti-IL-4 receptor monoclonal antibody or an isotype-matched antibody before either air or ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Apr
PMID:CD4+ T lymphocyte modulation of ozone-induced murine pulmonary inflammation. 769 18

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.
Mol Immunol 1993 May
PMID:Cytokine gene expression in mice undergoing chronic graft-versus-host disease. 848 82

In this paper we demonstrate the use of recombinant viral vectors derived from herpes simplex virus type 1 (HSV1) to transfer reporter genes in vitro into rat anterior pituitary cells grown in primary cultures and the anterior pituitary tumour cell lines GH3 and AtT20. The three vectors used were, tsK/beta-galactosidase (beta-gal), tsK/CRH and tsK/TIMP, the corresponding transgene products respectively being E. coli beta-gal, pre-procorticotropin releasing hormone (ppCRH), and the chimeric protein TIMP/Thy1 (tissue inhibitor of metalloproteinases (TIMP)/linked to the carboxy terminus of Thy1 which confers the addition of a glycolipid glycosyl-phosphatidylinositol anchor in the ER). Double labelling immunofluorescence experiments to detect reporter proteins and transduced cell types indicated that the three vectors could transfer and express the reporter genes in normal and tumour anterior pituitary cells. Virus infection of pituitary cells was characterised, and it was shown that infection with tsK/beta-gal at multiplicities of infection (MOI)=10, 100% of tumour and non-endocrine anterior pituitary cells expressed beta-gal, whereas 75% endocrine anterior pituitary cells expressed the transgene. Long-term expression studies after infection with tsK/beta-gal indicated that anterior pituitary cells in primary cultures expressed the transgene for significant longer periods than tumour anterior pituitary cells. Growth arrest by serum starvation markedly decreased the frequency of transgene expression in anterior pituitary cells following infection with tsK/beta-gal. Transgenic products expressed from tsK were targeted to their correct intracellular domain in both anterior pituitary cells in primary cultures and in pituitary tumour cell lines. We conclude that transgenes can be delivered into anterior pituitary cells in primary culture and pituitary tumour cell lines using tsK derived HSV1 vectors. The prospect of employing viral vectors to transfer genes into endocrine cells opens up the potential exploration of various molecular aspects of pituitary cell function both in vitro and in vivo, as well as the use of gene transfer into the pituitary for potentially therapeutic applications, such as the treatment of pituitary tumours.
Mol Cell Endocrinol 1998 Apr 30
PMID:Use of recombinant herpes simplex virus type 1 vectors for gene transfer into tumour and normal anterior pituitary cells. 970 88

The detection of T(H)1-type and T(H)2-type cells directly in situ would be of great value in the study of T(H) development and function in vivo. Transgenic mice expressing human Thy1 and mouse Thy1.1 under the control of the murine IFN-gamma and IL-4 promoters, respectively, have been generated. The hThy1(+) cells represent (with some temporal lag) most of the IFN-gamma-producing CD4(+) T-cells, while the mThy1.1(+) cells represent only a percentage of IL-4 secreting cells. This may be due to mono-allelic expression of the IFN-gamma and IL-4 genes. Since permeabilization is not required for the detection of the transgenic surface markers, these transgenic mice can facilitate the detection of T(H)1-type and T(H)2-type cells by flow cytometry with surface immunofluorescent staining. These surface markers should permit isolation of viable cells according to their T(H) type for adoptive transfer experiments, and may serve as a model system for tracing the development of T(H)1 and T(H)2-type cells in vivo.
Mol Immunol 2000 Apr
PMID:Transgenic mice expressing surface markers for IFN-gamma and IL-4 producing cells. 1100 Apr 2

Under normal conditions, kidney expresses Smad6 and Smad7 most abundantly among the organs of the body. To understand the physiological roles of these Smad expressions in the kidney, we first identified the sites of Smad6 and Smad7 expression in the rat kidney by in situ hybridization. The expression of Smad7 in the rat kidney was only observed in the glomeruli, while Smad6 was expressed in both the glomeruli and thick ascending limb of Henle's loop. In order to investigate whether Smad6 and 7 are also involved in the negative feedback loop of TGF-beta signaling in vivo, we examined the changes of mRNA levels of these Smads in the glomeruli of rat anti-Thy1 (1-22-3) nephritis, a model where the expression of TGF-beta in the glomeruli has been shown to be most up-regulated from day 4 to 14 after the antibody injection. Unexpectedly, 7 days after injection, the levels of Smad6 and Smad7 did not increase but rather decreased to approximately 70% of the levels on day 0. During that period, Smad7 immunostaining was observed in the glomerular endothelial cells (GEN) where Smad3 immunostaining was also observed. This suggested that Smad7 expression was not augmented by the TGF-beta signal in GEN in vivo in anti-Thy-1 nephritis. The absence of up-regulation of these inhibitory Smads may be involved in the pathogenesis of anti-Thy-1 nephritis.
Mol Cell Biol Res Commun 2000 Aug
PMID:Localization of Smad6 and Smad7 in the rat kidney and their regulated expression in the anti-Thy-1 nephritis. 1117 Aug 39


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