Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The membrane molecule termed "7F7-antigen" has been found to be involved in several examples of cell-cell interactions. This 85 kDa glycoprotein with a protein core of about 55 kDa contains N-linked and O-linked carbohydrates. It has an isoelectric point of 8.0-8.5 and is expressed on 20% of peripheral blood mononuclear cells, 35% of peripheral blood B-cells, follicular dendritic cells and vascular endothelium. It is also expressed on activated T-cells and its expression on B-cells, fibroblasts and monocytes increases after treatment with PWM, interferon-gamma and after three days culture, respectively. The MAb 7F7 used to define this antigen inhibits the initiation of T-cell proliferation induced by anti-CD3, PHA, ConA and (weakly) allogenic stimulator cells, but does not affect the growth of IL-2 dependent T-cells and does not interfere with the killing of PHA-blasts by allogenic IL-2 dependent T-cells. 7F7 also inhibits the binding of C3-coated sheep erythrocytes to B-cells, the PMA-induced aggregation of U937 and the binding of activated T-cells to fibroblasts. The 7F7-antigen is expressed on some non-Hodgkin lymphomas of B-cell differentiation, particularly those with follicular structure, but not on Burkitt's lymphoma, ALL or carcinomas of various tissues. It is, however, found on fibrous tissue surrounding infiltrating carcinoma cells. The expression of a melanoma antigen, P3.58, which was shown to be identical to 7F7-antigen correlates with stage and spread of invasive melanoma. It was concluded that the 7F7-antigen, which is probably related to a previously described adherence molecule (ICAM-1), is of biological importance for the initiation of T-cell responses. With the possible exception of melanoma its expression on neoplastic cells in vivo is unlikely to be of importance for the spread of malignant disease.
Mol Immunol 1988 Nov
PMID:Importance of an 85 kDa membrane glycoprotein for a variety of cell-cell interactions. 246 58

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from healthy donors, and their abilities to produce extracellular and cell-associated interleukin 1 (IL-1) in response to various activation stimuli were compared with those of autologous blood monocytes. The production of IL-1 alpha and IL-1 beta by monocytes and AM was examined by thymocyte co-stimulation assay and enzyme immunoassays (EIA). Results showed that when activated with lipopolysaccharide (LPS) or desmethyl muramyl dipeptide (norMDP), AM released much less extracellular IL-1 beta than did blood monocytes. In contrast, these activated AM produced more cell-associated IL-1 than did blood monocytes. When the IL-1 activity was examined by the thymocyte assay, the extracellular and cell-associated IL-1 produced by the two cell types were largely IL-1 beta and IL-1 alpha, respectively, as shown by antibody neutralization. The cell-associated IL-1 activity of AM induced by the synergistic actions of suboptimal concentrations of recombinant interferon-gamma (rIFN-gamma) and norMDP was also higher than that of autologous blood monocytes. Consistent with these findings on AM, macrophages generated in vitro by maturation of blood monocytes produced higher levels of cell-associated IL-1 activity than did freshly isolated monocytes. These observations suggest that AM may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell-associated IL-1 alpha.
Am J Respir Cell Mol Biol 1989 Dec
PMID:Normal human alveolar macrophages have more ability than blood monocytes to produce cell-associated interleukin-1-alpha. 248 61

The effects of biologic response modifiers such as interferon-gamma, tumor necrosis factor alpha (TNF), and retinoic acid on the human chorionic gonadotropin (hCG) secretion of cultured choriocarcinoma cells (JAR) and term placenta have been studied. Although the proliferation of JAR cells was not inhibited by these agents, retinoic acid and TNF markedly increased both the intracellular levels as well as the secreted amounts of hCG. In the case of the term placenta, only retinoic acid increased the hCG secretion into the culture medium, whereas interferon-gamma and TNF both markedly reduced secretion. The cytostatic agent etoposide (VP-16) was able to augment the hCG secretion on the choriocarcinoma cells but did not alter its production on term placenta. The The data presented indicate different mechanisms of regulation of hCG secretion in the normal and malignant trophoblast.
Mol Biother 1989
PMID:Modulation of secretion of human chorionic gonadotropin by biologic response modifiers on term placenta and choriocarcinoma cells. 251 40

The purpose of this study was to examine the effective anti-metastatic activity by multiple i.v. administrations of mouse recombinant interferon-gamma (IFN-gamma) against pulmonary metastases of 3LL or B16-BL6 melanoma cells after surgical excision of primary tumors. Multiple treatments with IFN-gamma reduced effectively the incidence of pulmonary tumor metastases. Repeated 4 consecutive treatment modalities with IFN-gamma showed remarkable reduction of lung tumor colonies, and also rendered alveolar macrophages (AM) cytotoxic against B16-BL6 cells. In contrast, 14 consecutive administrations of IFN-gamma at any doses (10(2) and 10(3) U/mouse) could not activate macrophages to become cytotoxic, but were effective in regressing metastases. Thus, antimetastatic activity of IFN-gamma may be due to the stimulation of host immune defense systems such as induction of tumoricidal macrophages, presumably the direct antiproliferative action to tumor cells, or both actions under the appropriate administration conditions. We found that the systemic administration of IFN-gamma under appropriate multiple treatment modalities results in the reduction of the lung metastases and can activate AM to become tumor cytotoxic at relatively low doses (10(2) U). High-dose IFN-gamma in the multiple administration schedule was also effective for the reduction of lung tumor colonies, but strongly suppressed the nonspecific immune function and could not activate tumoricidal properties of AM.
Mol Biother 1989
PMID:Effect of systemic administration of mouse recombinant interferon-gamma on the lung tumor metastases in mice. 251 71

The fungicidal and bactericidal activities of human alveolar macrophages (AM) and peripheral blood monocytes (PBM) from 18 healthy volunteers were evaluated. The results showed that AM were able to phagocytize and kill Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. However, killing of the bacteria was already complete in 2 h, whereas killing of Candida required 4 to 6 h despite an early phagocytosis of yeast cells. The fungicidal activity of freshly collected AM and PBM was also tested after effector cell exposure to interferon-gamma (IFN-gamma), interleukin-1-alpha (IL-1 alpha), endotoxin lipopolysaccharide (LPS), or interleukin 2 (IL-2). It was found that treatment with IFN-gamma, IL-1 alpha, or LPS significantly augmented macrophage and PBM candidacidal activity, whereas the addition of IL-2 was ineffective. We also evaluated killing of C. albicans by AM cultured in vitro for different times. While phagocytosis was apparently unaffected, the candidacidal activity progressively decreased over the in vitro culture period, an effect that was largely reversed by cell exposure to IFN-gamma, IL-1 alpha, or LPS. In an experimental model in which mice infected with an agerminative C. albicans strain (PCA-2) resisted lethal microbial challenge, freshly harvested AM showed increased cytotoxic activity to Aspergillus fumigatus in vitro as well as enhanced IL-1 production. In conclusion, present data confirm the crucial role of AM in the surveillance of bacterial and fungal infections and indicate that treatment of these cells with IFN-gamma or IL-1 alpha is able to enhance their antimicrobial capability.
Am J Respir Cell Mol Biol 1989 Jul
PMID:Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha. 251 51

We examined the activities of activated lymphocytes, interferon-gamma (IFN-gamma), and interleukin 2 (IL-2) in adoptive immunotherapy of pulmonary metastases. Pulmonary metastases produced in Balb/c mice by a single tail-vein injection of 5 X 10(5) murine sarcoma (MCB8) tumor cells on day 0 were treated with combinations of Con A-activated lymphocytes (CAL) (3 X 10(7) cells on days 3 and 7), IL-2 (5 X 10(4) U three times a day on days 3 to 8), and IFN-gamma (5 X 10(4) U/mouse on days 1 to 8). Treated tumors contained increased numbers of infiltrating Thy-1.2+ lymphocytes and a predominance of L3T4+(CD4+) lymphocytes. The level of expression of class I and class II MHC antigens by tumor cells in the lung was increased after treatment. Mice that received CAL + IL-2 + IFN-gamma showed approximately 80% reduction in tumor burden as compared to controls (P = 0.001). Mice treated with IL-2 + CAL, or IL-2 + IFN-gamma, displayed approximately 50% reduction (both P less than 0.02 as compared to triple therapy), whereas IL-2, IFN-gamma, or CAL administered as single agents had little effect on pulmonary metastases. We conclude that adoptive immunotherapy with activated lymphocytes and IL-2 is enhanced by IFN-gamma.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma. 251 74

Corticosteroids have multiple effects on immune and inflammatory responses and decrease host resistance to a broad range of microorganisms. Resident tissue macrophages have been proposed as a target for the immunosuppressive effects of corticosteroids and are important in host defense against infections. During infection-induced immune responses, macrophages are activated after exposure to interferon-gamma (IFN-gamma), and class II major histocompatibility (Ia) antigens on their surface are increased. We investigated the effect of orally administered corticosteroids on alveolar macrophages, the resident macrophages of the lung parenchyma. We hypothesized that corticosteroids would inhibit the activation of alveolar macrophages and measured induction by IFN-gamma of Ia antigens as a marker of cell activation. Alveolar macrophages from normal and corticosteroid-treated rats were exposed to recombinant murine IFN-gamma (rMuIFN-gamma) in vitro and assayed for Ia transcription and surface Ia expression. Ia mRNA accumulation was induced in alveolar macrophages from normal and corticosteroid-treated rats after exposure in vitro to rMuIFN-gamma. Furthermore, rMuIFN-gamma increased surface expression of Ia proteins on alveolar macrophages from corticosteroid-treated rats, although to a lesser extent than on cells from control rats. Finally, surface Ia expression could also be increased in vivo by exposure of corticosteroid-treated rats to an aerosol containing rMuIFN-gamma. These results demonstrate that administration of oral corticosteroids, while establishing a state of immunosuppression in rats, does not abolish responsiveness of rat alveolar macrophages to rMuIFN-gamma. We speculate that IFN-gamma-induced augmentation of phagocytic cell function may constitute an important therapeutic modality to treat complications of immunodeficiency.
Am J Respir Cell Mol Biol 1989 Dec
PMID:Interferon-gamma increases alveolar macrophage Ia antigen expression despite oral administration of dexamethasone to rats. 251 78

The inhibitory effects of recombinant porcine interferon-gamma (IFN gamma) on human CG (hCG)-stimulated testosterone production, and on mRNA concentrations of cholesterol side-chain cleavage (P450scc) and 17 alpha-hydroxylase/C17-20lyase (P450c 17) were investigated using porcine primary Leydig cell culture as a model. After preincubation of Leydig cells for 24 h with 1000 pM IFN gamma, hCG-stimulated (10 ng/ml, 2 h) testosterone production was inhibited by 50%, whereas no significant changes were seen in hCG-stimulated cAMP production. Incubation with 10 microM 5-cholestene-3 beta,22(R)-diol or 10 microM 5-cholestene-3 beta,20 alpha-diol together with hCG (10 ng/ml, 2 h) reversed most of the inhibitory effect of IFN gamma, suggesting that IFN gamma inhibits P450scc activity, possibly by inhibiting the substrate (cholesterol) availability for P450scc. Incubation with IFN gamma also decreased basal concentrations of P450scc (45%) and P450c 17 (35%) mRNA, although these changes probably did not contribute to the decreased testosterone production. Long-term treatment with hCG (100 ng/ml, 24 h) increased P450scc mRNA (3- to 4-fold) and P450c 17 mRNA (4- to 5-fold) concentrations. Simultaneous treatment with IFN gamma attenuated these hCG-induced increases in P450scc mRNA (50%) and P450c 17 mRNA (40-100%) concentrations, as well as in testosterone production (77%). This inhibition of testosterone production could only be partly reversed by the hydroxylated cholesterol derivatives. This suggests that in addition to possible suppression of cholesterol availability, decreased P450scc and/or P450c 17 activities (through decreased mRNA concentrations) were also involved in the IFN gamma suppressed steroidogenic capacity of porcine Leydig cells during long-term hCG stimulation.
Mol Endocrinol 1989 Jun
PMID:Interferon-gamma inhibits steroidogenesis and accumulation of mRNA of the steroidogenic enzymes P450scc and P450c17 in cultured porcine Leydig cells. 254 1

The human Me14-D12 antigen is a cell surface glycoprotein regulated by interferon-gamma (IFN-gamma) on tumor cell lines of neuroectodermal origin. It consists of two non-convalently linked subunits with apparent mol. wt sizes of 33,000 and 38,000. Here we describe the molecular cloning of a genomic probe for the Me14-D12 gene using the gene transfer approach. Mouse Ltk- cells were stably cotransfected with human genomic DNA and the Herpes Simplex virus thymidine kinase (TK) gene. Primary and secondary transfectants expressing the Me14-D12 antigen were isolated after selection in HAT medium by repeated sorting on a fluorescence activated cell sorter (FACS). A recombinant phage harboring a 14.3 kb insert of human DNA was isolated from a genomic library made from a positive secondary transfectant cell line. A specific probe derived from the phage DNA insert allowed the identification of two mRNAs of 3.5 kb and 2.2 kb in primary and secondary L cell transfectants, as well as in human melanoma cell lines expressing the Me14-D12 antigen. The regulation of Me14-D12 antigen by INF-gamma was retained in the L cell transfectants and could be detected both at the level of protein and mRNA expression.
Mol Immunol 1989 Jun
PMID:A novel interferon-gamma regulated human melanoma-associated antigen, gp33-38, defined by monoclonal antibody Me14-D12. II. Molecular cloning of a genomic probe. 254 4

From a panel of IgG1 myeloma proteins, only one was found to interact with human monocyte FcR in a manner similar to that of polyclonal IgG. This protein was used in binding studies involving human macrophage Fc receptors. A monomeric fraction depleted of dimeric and polymeric IgG1 was crosslinked with bis-diazonium benzidine, and a fraction highly enriched in cross linked IgG1 dimers was radiolabeled. Labeled monomeric and dimeric IgG were allowed to interact with monocytes that had matured to macrophages in vitro. The association with macrophages at 4 degrees C, in the presence of cytochalasin B, reached a plateau after 6 hr. The dissociation induced by excess unlabeled IgG followed similar kinetics as the association, but 20-30% of the bound IgG could not be dissociated. Under equilibrium conditions, evidence for a single FcR population binding monomeric IgG was obtained, the Kd being in the range of 12-42 nM. In contrast, the binding of dimeric IgG was more consistent with a model assuming two populations of binding sites when appropriate curve-fitting calculations were applied. The high-affinity FcR population had a Kd in the range of 0.8-3.5 nM, whereas the Kd of the low-affinity FcR population was in the range of 28-85 nM. When macrophages had been pre-treated with recombinant interferon-gamma, the expression of high-affinity sites was increased by a factor of 1.5-3, but the number of low-affinity sites was not augmented. Cytofluorographic analyses confirmed the increased expression of high-affinity FcR, binding fluoresceinating murine IgG2a. The expression of CD16, a low-affinity FcR expressed on neutrophils, NK cells and macrophages, as well as the expression of the complement receptor type III was little influenced by the rIFN-gamma pretreatment.
Mol Immunol 1988 Aug
PMID:Monomeric and dimeric IgG1 as probes for assessing high-affinity and low-affinity receptors for IgG on human monocyte-derived macrophages and on activated macrophages. 297 17


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