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ABSTRACT: Members of the inhibitor of apoptosis protein (IAP) family including survivin, are expressed in many tumors. However, age-related changes in their expression in cancer have not been clarified. Thus, we investigated the expression of mRNA-coding for IAP family proteins in colon cancer samples from young (<70 years of age) and elderly (>70 years) patients by real-time quantitative RT-PCR. Samples were collected from cases with well-differentiated adenocarcinoma or moderately differentiated adenocarcinoma and their adjacent normal epithelial tissue. Well-differentiated adenocarcinoma tended to express higher levels of survivin than normal mucosa, and expression in moderately differentiated adenocarcinoma was significantly greater than in normal mucosa in samples from both groups of patients ( p<0.05, respectively). When samples were compared between the different age groups, the normal mucosa exhibited similar levels of survivin expression. However, samples from older patients showed a significantly higher level of expression than those from younger patients in well and moderately differentiated adenocarcinomas ( p<0.05, respectively). In contrast, the levels of expression of cIAP1, cIAP2, and NAIP in the cancerous tissues were lower than those found in normal mucosa regardless of age. As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group ( p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group ( p<0.05). XIAP expression was similar in normal and cancerous tissues in both the young and elderly groups. These results suggest that the expression of IAP family proteins, especially survivin, is associated with the age-related biological characteristics of colon cancer.
Cancer Immunology and Immunotherapy 10/2004; 53(9):770-6. · 3.70 Impact Factor
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ABSTRACT: Ecotropic infection by Murine leukemia virus (MuLV) infection is initiated by the interaction between the receptor-binding domain of the viral surface glycoprotein (SU) and the cell-surface receptor, mCAT-1. To study the in vivo localization of viral binding site in mice, green fluorescence protein (GFP)-tagged Friend SU (F-SU/GFP) was incubated with tissue sections. Lymphohematopoietic organs and a part of the glandular tissues of C3H as well as C57BL/6 mice revealed positive signals for F-SU/GFP binding on the cell surface. In contrast, C4W mice, which is a partial congenic mouse strain carrying the Fv-4 (r) gene on a BALB/c genetic background, exhibited negative signals in most of the organs except for a very weak binding in the pancreas. The expression of mCAT-1 mRNA determined by reverse transcriptase (RT)-polymerase chain reaction (PCR) revealed a similar distribution in C3H, C57BL/6 and C4W mice. Most of the organs including lymphohematopoietic organs and glandular organs revealed significant expression of mRNA for mCAT-1 gene, while the liver, heart and muscle did not. The results from binding assay were consistent with the fact that Friend MuLV-induced pathogenesis was usually associated with lymphohematopoietic systems, although mRNA expression for mCAT-1 was rather ubiquitous. The discrepancy between F-SU/GFP binding and mRNA expression for mCAT-1 in lymphohematopoietic organs of C4W mice would support the receptor interference effect by the Fv-4 (r) gene causing the resistance of C4W mouse to Friend MuLV infection.
Archives of Virology 07/2003; 148(6):1175-84. · 2.11 Impact Factor
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ABSTRACT: At the initial stage of retroviral infection, virion envelope glycoprotein (env product) binds to cell surface receptors. Cells infected with retrovirus or into which the env gene was introduced, become resistant to superinfection by other retroviruses with the same receptor specificity, a phenomenon known as receptor interference. We have demonstrated previously that the introduction of an env gene from a truncated endogenous ecotropic murine leukemia virus (MuLV), the Fv-4 resistance (Fv-4r) gene, into the bone marrow hematopoietic cells of Fv-4 sensitive (Fv-4s) mice protected mice from ecotropic retrovirus-induced disease. Using the gene transfer system under the control of the retroviral vector and bone marrow transplantation (BMT), here we could show that the expression of an introduced Fv-4r gene in hematopoietic cells continued for more than 1 year after BMT. To determine the inhibitory mechanism of Fv-4r env gene expression against FLV-infection in this model system, peripheral blood mononuclear cells (PBMCs), or spleen cells from chimeras with various degrees of env-expression, were mixed with green fluorescence protein (GFP)-conjugated Friend MuLV envglycoprotein (GFP-Fr-ENV). The amount of GFP-Fr-ENV bound to these cells inversely correlated with the expression intensity of the transduced env gene indicating the receptor interference effect. Next, to see whether transduction of the Fv-4r gene would protect an immunosuppressed host from FLV-induced leukemogenesis, we generated immunocompromised chimeras by transplanting env-transduced bone marrow cells into a thymectomized host. These chimeras also resisted FLV-induced leukemogenesis, indicating that receptor interference-based gene therapy could become a therapeutic basis for immunodeficiency virus-induced diseases in vivo.
Leukemia 12/2001; 15(11):1779-84. · 9.56 Impact Factor
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ABSTRACT: We examined the effect of two Japanese herbal medicines (Kampo-Hozai) on immunological functions and anti-tumor activity in old mice. Hochu-ekki-to (TJ-41) was remarkably effective in the restoration of impaired immune functions of old mice, in terms of number of T cells and NK cells, and anti-SRBC antibody response, while it was not effective in enhancing immune functions of young mice. Juzen-taiho-to was also effective in increasing the number of T cells, remarkably, and NK cells, slightly, in the aged mice. While a significant increase was not observed in young mice. NK activity increased both in young and old mice with the treatment of TJ-48. A significant decrease was observed in metastatic pulmonary colonies of B16 melanoma cells both in young and old mice treated with Juzen-taiho-to for 16 weeks. These results suggested that some of Japanese herbal medicines were useful in restoration of impaired immune functions of old mice and could be recommended for human elderly.
Mechanisms of Ageing and Development 04/2001; 122(3):341-52. · 3.44 Impact Factor
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ABSTRACT: Susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the C3H/He (C3H)-->C57BL/6 (B6) radiation bone marrow chimeras of various age groups, and the effect of aging of host mice on the susceptibility was determined. The bone marrow chimera system provided the various age of FLV-resistant host mice (B6) possessing the same age of FLV-susceptible target cells from C3H mice. Using this system, we could determine the aging effect on the host resistancy against FLV without an influence of the aging effect on target cells. First, the young C3H-->young B6 chimeras and young C3H-->old B6 chimeras were compared. The young-->old chimeras were more susceptible to FLV-induced acute disease than the young-->young chimeras. The spleen CD4+ as well as CD8+ T cells were reduced in young-->old chimeras compared with young-->young chimeras. Similarly, the old C3H-->old B6 chimeras were more susceptible than old-->young chimeras and revealed the lower CD4+ T cell ratio in the spleen. Discussion was made on the possible implication of these findings on the role of T cells in age-related change of resistance to FLV-induced leukemogenesis.
Mechanisms of Ageing and Development 03/2001; 122(2):219-32. · 3.44 Impact Factor
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ABSTRACT: The purpose of this study was to verify the WHO classification of thymic tumors using immunohistological methods, and to discover whether these methods can be applied to differentiate thymoma from squamous cell carcinoma (SCC) of the esophagus and the lung. Twenty-nine thymoma cases were classified according to WHO and were then immunohistologically examined for the positivity of these molecules. All thymoma cases investigated in this study were positive for IL-1R, and most of them were also positive for bek. In contrast, UH-1 was highly positive in B1 and B2 type thymomas, but negative or weakly positive in A, AB and B3 type thymomas. Twelve esophageal cancers and 21 lung cancers were also examined for the positivity of the same molecules. All esophageal cancers were negative for UH-1. Three of 12 cases were weakly positive for IL-1R, and four of these 12 cases were also weakly positive for bek. Twelve of 21 lung cancer cases were adenocarcinomas, all of them negative for IL-1R, bek and UH-1. Nine of 21 lung cancer cases were SCCs, all of them negative for UH-1. Eight of nine SCC cases were strongly positive for IL-1R, while seven of these were weakly positive for bek. We conclude that the WHO classification of thymic tumors is still valid as demonstrated by immunohistological analysis and that the positivity of UH-1, IL- 1R and bek might be helpful in differentiating thymoma from SCC of the esophagus and the lung.
Pathology - Research and Practice 02/2001; 197(9):611-9. · 1.21 Impact Factor
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ABSTRACT: Expression of mRNA protein tyrosine phosphatases (PTPs) was surveyed in an esophageal cancer cell line by RT-PCR using degenerate primers. The mRNAs for eight kinds of PTPs were expressed in the cell line. We examined mRNA expression of these PTPs in 12 cases of esophageal cancer by Northern analysis. Significant signals were obtained for three kinds of PTPs, PTP1B, PTPH1, and PTPD1. The magnitude of expression of each PTP was measured as the ratio of the signal intensity of each PTP to that of a control gene (NADPH), and the ratio was then compared to normal mucosa around the cancer lesion. Among the three kinds of PTPs, the expression of PTP1B mRNA was significantly depressed in cancer lesions compared with that in the surrounding normal mucosa. In contrast, the expression of PTPH1 mRNA was significantly increased in cancer lesions compared with that in normal mucosa. PTPD1 did not show any significant trend in comparisons of cancer and surrounding normal mucosa. The results suggest that PTP1B and PTPH1 are engaged in opposing signaling pathways, the tumor-suppressive and tumor-promoting pathways, respectively, in esophageal carcinogenesis.
Experimental and Molecular Pathology 07/2000; 68(3):187-95. · 2.42 Impact Factor
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ABSTRACT: We immunohistologically investigated 76 cases of primary colorectal cancer and 13 cases of adenoma to clarify the relationship of MHC class II expression with the grade of differentiation, the density of tumor-infiltrating lymphocytes, and the incidence of metastasis to lymph nodes. MHC class II expression was mostly negative in normal colonic epithelium. In contrast, 32 out of 76 cases (42%) of cancer and five out of 13 cases (38%) of adenoma were positive for MHC class II. MHC class II expression was higher in well-differentiated than in poorly differentiated adenocarcinoma. The density of infiltrating lymphocytes was higher in cancer than in the normal mucosa, and higher in MHC class II-positive tissues than in negative lesions. The incidences of lymphatic invasion and cancer metastasis to lymph nodes were definitely higher in MHC class II-negative cancers than in MHC class II-positive cancers. MHC class II was rarely expressed in metastatic cancer cells of lymph nodes. These results indicated that the loss of MHC class II is correlated with the incidence of metastasis to regional lymph nodes.
Pathology - Research and Practice 02/2000; 196(12):807-15. · 1.21 Impact Factor
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ABSTRACT: Young and old C57BL/6 male mice were given a diet containing a high dose of vitamin E (VE treatment) and its effect on the immune system was examined before and after the exposure to restraint stress. The VE treatment per se gave rise to a slight increase of splenic T cells in percentage and a significant enhancement of Con A response of spleen cells in young, but not in old mice. The VE treatment also resulted in the enhancement of production of IL-2 and IFNgamma in young, but not in old mice. Restraint stress led to thymic involution in both young and old mice. This thymic involution was not ameliorated by the VE treatment. Percentage of splenic T cells and their mitogenic response decreased just after the stress, but soon rebounded over the control level. The VE treatment further enhanced the recovery after the stress in young mice, but on the contrary suppressed the recovery in old mice. The results in the present study suggested that the VE treatment was effective in the prevention of immunological decline of young mice before and after the exposure to the stress. On the other hand, such a preventive effect was not observed in old mice that were already in the depressed state of immunological functions.
Experimental Gerontology 12/1999; 34(7):853-62. · 3.74 Impact Factor
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ABSTRACT: Aged mice treated with a low dose of cyclophosphamide (CY) showed significantly enhanced immune capacity in cellular proliferation and antibody response. In these mice, total cell numbers were increased both in the thymus and spleen, compared to those in non-treated mice. Treatment with a low dose of CY induced apoptosis of thymocytes in the atrophic thymus of the aged mice, being followed by an increase of proliferation of thymocytes and leading to an increase of thymocytes and splenic T cells. Treatment with a high dose of CY also induced apoptosis in the thymus, but suppressed the proliferative capacity, therefore not leading to an enhancement of immune capacity. In young mice, however, CY suppressed immune capacity regardless of the dose. Thymocytes and splenic T cells of young mice were more susceptible to CY than those of old mice and were decreased in number after the treatment with even a low dose of CY.
Mechanisms of Ageing and Development 12/1999; 111(1):1-12. · 3.44 Impact Factor
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ABSTRACT: Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). We have studied the expression of the inducible NOS (iNOS) by bone marrow cells from the patients with myelodysplastic syndromes (MDS) at the mRNA level by RT-PCR assay and at the protein level by immunohistochemical staining using a specific anti-iNOS monoclonal antibody. The iNOS message was present in 92% of bone marrow tissues from MDS patients (11 out of 12) by an examination using RT-PCR. Basically, iNOS message was negative or very weak in control (1/9) and AML (0/7) cases. This was supported by immunohistochemical findings that the iNOS was positive in most of the bone marrow samples from MDS patients (9 out of 12), while bone marrow cells of control (O out of 12) and AML (O out of 5) cases were basically negative. Double immunostaining for CD68 antigen, which is a marker for macrophage lineage cells, and iNOS was performed on MDS bone marrow sections. iNOS was dominantly localized to bone marrow macrophages, although a part of myeloid cells were also positively stained with anti-iNOS antibody in a part of cases. These results indicated that there is some in vivo induction of iNOS expression for local NO production that might be involved in the dysregulation of hematopoiesis in bone marrow of MDS.
Leukemia 06/1999; 13(5):699-703. · 9.56 Impact Factor
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ABSTRACT: Spleen cells from young and old C57BL/6 mice were stimulated with a combination of anti-CD3 and anti-CD28 antibodies, and the profile of cytokine production was examined by two different methods; the concentrations of cytokines as measured by ELISA, and identification of cytokine-positive cells by flow cytometry. The ELISA method revealed that IL-2 production by spleen cells after stimulation was significantly lower in the old mice compared to the young mice. while IFN-gamma production was the reverse. The flow cytometric analysis showed that the percentage of IL-2 positive cells in spleen cells after the stimulation was significantly lower in the older mice than in the young mice, and vice versa for the percentage of IFN-gamma-positive cells. Regarding the T cell subsets, CD4+ T cells were a major source of IL-2 in both the young and old mice. IL-2-positive cells in both CD4+ and CD8+ T cells showed a significant decrease with age. On the contrary, CDX T cells were the major source of IFN-gamma. An age-related increase of IFN-gamma positive cells was observed in both CD4+ and CD8+ T cells. CD4 T cells were the major source of IL-4, and the percentage of IL-4-positive CD4+ T cells also increased with age, although the level of IL-4 production was modest in C57BL/6 mice compared with IL-2 and IFN-gamma. Such age-related changes of cytokine production are presumed to play an important role in the alteration of immunological capacity with age.
Experimental Gerontology 05/1999; 34(2):231-42. · 3.74 Impact Factor
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ABSTRACT: Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We have demonstrated previously that bone marrow chimeras in which hematopoietic cells were replaced with cells expressing Fv-4 resistant (Fv-4r) gene product became refractory to Friend leukemia virus (FLV)-induced leukemogenesis. To induce in vivo resistance against retrovirus-induced diseases by retroviral vector-mediated gene transduction, we introduced Fv-4 env gene into bone marrow cells of FLV-susceptible C3H/He (C3H) mice with retroviral vector (pLSF) derived from murine Friend spleen focus forming virus (SFFV) and the cells were transplanted into lethally irradiated C3H mice. After the bone marrow transplantation, Fv-4r gene product was successfully expressed on erythroid and myeloid cells, while lymphoid cells were only weakly expressing Fv-4r gene product. The C3H mice expressing relatively higher amounts of Fv-4r gene product were rendered resistant to FLV-induced erythroleukemia, while mice expressing lower amounts of the Fv-4r gene product were still susceptible. Effective protection of FLV-induced leukemia in these mice suggested that the Fv-4r gene expression by erythroid cells that were the major target of FLV infection might be critical for resisting FLV-induced leukemia. Thus, gene therapy model by transducing Fv-4r env gene using bone marrow transplantation would provide a useful protection model system of retrovirus-induced diseases.
Experimental Hematology 03/1999; 27(2):234-41. · 2.90 Impact Factor
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ABSTRACT: Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes (MDS) was demonstrated on frozen sections using the terminal deoxytransferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS cases showed expression of Fas mRNA (12/12) and most exhibited an expression of FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive signals for Fas and FasL mRNA, however, a very weak band was detected in three cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR. Immunohistochemical examination revealed positive staining for Fas (11/12) and FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15) antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive cells which were macrophage lineage cells, did not express Fas antigen strongly. In contrast, positive staining for FasL was detected in hematopoietic cells and CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas-FasL system plays an important role in inducing apoptosis in the bone marrow of MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction) and/or paracrine (hematopoietic cell-stromal cell interaction) manner.
Leukemia 05/1998; 12(4):486-92. · 9.56 Impact Factor
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ABSTRACT: The administration of corticosteroids induced apoptosis of thymocytes in vivo. Among various adhesion molecules examined, vascular cell adhesion molecule-1 (VCAM-1, CD106) was shown to be strongly expressed in these apoptotic cells. Flow cytometric analysis also showed the expression of VCAM-1 in apoptotic thymocytes. An RT-PCR study demonstrated the expression of VCAM-1 mRNA in thymocytes. Splenic lymphocytes and other lymphoid cell lines also expressed VCAM-1 during the process of apoptosis. VCAM-1 mRNA expression was also observed in RT-PCR performed on these cell lines.
Pathobiology 02/1998; 66(6):274-83. · 1.18 Impact Factor
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ABSTRACT: To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-alpha was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-gamma was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-gamma mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-alpha and occasionally IFN-gamma by bone marrow macrophages.
Leukemia 01/1998; 11(12):2049-54. · 9.56 Impact Factor
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ABSTRACT: Earlier studies from this laboratory using Thy 1 congenic B10 strain mice suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow in addition to the destruction of the thymus after fractionated whole body X-irradiation (IR) are the two main critical factors that cause differentiation arrest of initially repopulating intrathymic radio-resistant T cell progenitors, which then lead to the appearance of preneoplastic, prelymphoma cells, and eventually to highly neoplastic thymic lymphomas under the influence of the thymic environment. In order to explore the significance of the depletion (or reduction) of T cell progenitors in the bone marrow during pathogenesis of radiation-induced thymic lymphomas, we compared the pool size of pre T cells in the bone marrow and the spleens as well as the profiles of the regenerating thymocyte populations between thymic lymphoma induction-susceptible B10 and -resistant C3H strain mice following irradiation. The results indicated that irradiation severely depleted the pre T cells in the bone marrow and the spleens of both lymphoma induction-susceptible and -resistant mice. They also showed that in C3H mice the differentiation and maturation of intrathymic T cell progenitors which initially repopulated the depleted thymus seemed to proceed normally in spite of the poor cellularity, while this process was greatly suppressed in B10 mice. These data indicate that a depletion of pre T cells in the bone marrow combined with atrophy of the thymus in the irradiated mice is necessary, but not sufficient for development of thymic lymphoma. Implication of these findings on the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.
International Journal of Radiation Biology 09/1997; 72(2):191-9. · 2.28 Impact Factor
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ABSTRACT: Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). The Fv-4' env antigen that binds to the cell surface of Fv-4'-bearing C3H cells was found in sera from normal Fv-4'-bearing C4W mice. The serum Fv-4' env antigen binds to ecotropic MuLV receptors, shown by specific binding to transfectant cells expressing ecotropic MuLV receptors but not to parental mink cells. To determine whether the binding of Fv-4' env antigen to the putative MuLV receptors would block FLV infection, C3H thymocytes or spleen cells that had been preincubated with C4W serum were mixed with FLV and the subsequent production of MuLV specific antigens was examined. C3H thymocytes or spleen cells treated with C4W serum became refractory to binding by FLV. These results provide evidence that the Fv-4' env antigen is released from C4W-derived cells in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with FLV. The implication of these findings for gene therapy of retrovirus-induced disease such as acquired immune deficiency syndrome (AIDS) is discussed.
Leukemia 05/1997; 11 Suppl 3:230-2. · 9.56 Impact Factor
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ABSTRACT: Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We demonstrated previously that the Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released from Fv-4r-bearing BALB/c-Fv-4Wr (C4W) mouse-derived cells into serum in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with Friend leukemia virus (FLV) by receptor interference. This unique resistance mechanism against retroviral infection might provide a possible therapeutic model system of human retroviral infection such as AIDS. To further investigate the Fv-4r gene action in vivo, we examined the distribution and character of Fv-4r env antigen in serum and systemic organs from C4W mice. The Fv-4r env antigen was immunohistochemically localized to the lympho-hematopoietic cells and exocrine glandular cells, such as those of the salivary gland and pancreas. Using immunoprecipitation followed by Western blotting, we determined two types of gp70-related Fv-4r env antigen in the serum of C4W mice, showing molecular weights of either 70-75 kDa and 80-85 kDa. When thymocytes from Fv-4 susceptible gene (Fv-4r)-bearing C3H mouse were mixed with C4W mouse serum, the 70-75k Da molecule of the C4W serum dominantly bound to C3H thymocytes and thus contributed to receptor interference function. Using immunoelectron microscopy, Fv-4r env antigen was mainly localized to the cell surface membrane of thymic lymphoid cells, while acinar cells of the salivary gland possessed Fv-4r env antigen in the endoplasmic reticulum (ER) as well as on the cell surface membrane. These data indicate that several glandular organs, as well as lymphohematopoietic organs of C4W mice, may contribute to the production of cell-free Fv-4r env antigen, resulting in protection of cells from infection with FLV by receptor interference.
Experimental Hematology 11/1996; 24(12):1423-31. · 2.90 Impact Factor
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ABSTRACT: Resistance to retroviral infection is often regulated by multiple genes that control different aspects of the host-virus interaction. Genetically distinct inbred strains of mice differ in their susceptibility to retrovirus and have allowed the identification of several host-resistant loci that regulate the host defense mechanism to retroviral infection. Using the murine retrovirus infection system, a therapeutic model has been developed of retrovirus infection in association with the resistant mechanism of host genes. The most effective result achieved with the model was when using bone marrow transplantation of retrovirus-resistant cells with receptor interference function, which was genetically defined by the Fv-4 resistant gene. The possible application of these findings to the gene therapy of retrovirus-induced disease of humans is discussed.
Pathology International 11/1996; 46(10):719-25. · 1.62 Impact Factor
