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MECHANISM OF GENETIC RESISTANCE TO IMMUNE SUPPRESSION BY FRIEND LEUKEMIA-VIRUS - ROLE OF MARROW-DEPENDENT CELLS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP3期276卷 217-228页

作者： KUMAR, V ECKNER, RJ BENNETT, M BOSTON UNIV SCH MEDDEPT PATHOLBOSTONMA 02118

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REVERSAL OF IMMUNOSUPPRESSION INDUCED BY MURINE LEUKEMIA VIRUSES

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP3期276卷 431-441页

作者： BENDINELLI, M TONIOLO, A FRIEDMAN, H UNIV PISA INST MICROBIOLI-56100 PISAITALY ALBERT EINSTEIN MED CTR DEPT MICROBIOLPHILADELPHIAPA 19141

BALB/c mice infected with Rowson-Parr virus, a lymphatic leukemia virus isolated from the Friend complex, undergo a rapid depression of antibody response. Spleen cells from these mice in culture show a similar deficit in the response to stimulation with sheep red cells and inhibit the reactivity of normal splenocytes. In an attempt to reverse this immunosuppression, near normal responses were obtained in vitro from infected splenocytes by increasing antigen dose, by adding E. coli lipopolysaccharide, or, more effectively, by cocultivating with small numbers of unfractionated or T cell-depleted peritoneal exudate cells (PC), whereas other manipulations proved ineffective. PC did not prevent the inhibition of normal splenocytes by infected spleen cells, but exhibited substantial restorative activity in vivo. In similar experiments, the immunosuppression exerted by the entire Friend complex could be reversed by PC in vitro but not in vivo. These results indicate that a functional deficit of macrophages may be partially responsible for the immunological impairment induced by leukemia viruses and suggest rational approaches to evaluate the relevance of this impairment to oncogenesis.

关键词：抗体生成/药物作用抗原腹水液/免疫学剂量效应关系免疫红细胞/免疫学弗林德鼠白血病病毒免疫球蛋白M/生物合成免疫抑制法白血病实验性/免疫学脂多糖类/药理学巨噬细胞/免疫学小鼠近交BALBC 脾/免疫学肿瘤病毒感染/免疫学动物小鼠

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CHROMATIN AS A TEMPLATE FOR RNA-SYNTHESIS INVITRO

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1975年第1期72卷 194-199页

作者： GRONER, Y MONROY, G JACQUET, M HURWITZ, J ALBERT EINSTEIN COLL MED DEPT DEV BIOL & CANCDIV BIOL SCIBRONXNY 10461

RNA transcribed in vitro from myeloblast chromatin by exogenously added RNA polymerase B predominantly consists of short chains that remain in hybrid structure with the template; the remainder of the product is free RNA of heterogeneous size. Addition of polyanions during synthesis caused an increase in the size and amount of free RNA with a concomitant decrease in the proportion of small RNA. The large molecular weight RNA is derived from the short RNA chains, which are synthesized de novo during the reaction in vitro. The effect of polyanions on the size and nature of the product may be related to structural changes induced in the template rather than to an inhibition of nuclease activity.

关键词：禽成髓细胞白血病病毒/代谢离心法梯密度鸡染色质/代谢 DNA 单链/代谢 DNA 病毒/代谢指导DNA的RNA聚合酶类/代谢大肠杆菌弗林德鼠白血病病毒 HeLa细胞肝素/药理学分子量核酸构象蛋白质生物合成 RNA 病毒/生物合成模板遗传转录遗传动物人类

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CONSTITUTIVE SYNTHESIS OF GLOBINS WITHIN MOST OF THE MEMBERS OF AN UNINDUCED, PROLIFERATING POPULATION OF FRIEND-ERYTHROLEUKEMIC CELLS

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DEVELOPMENTAL BIOLOGY 1979年第2期69卷 576-588页

作者： REEVES, R CSERJESI, P Department of Zoology University of British Columbia Vancouver B. C. Canada V6T 1W5

The proteins synthesized by Friend [mouse] erythroleukemic cells (clone 745), before and after they are induced by treatment with dimethylsulfoxide to undergo overt erythroid maturation, were analyzed by a number of biochemical methods. None of these techniques revealed any consistent observable differences (other than quantitative variations in the concentrations of particular proteins) between the uninduced and the induced cells. Various classes of cellular proteins (whole cell, cytoplasmic and nuclear) appear to be very similar in the 2 types of cells when analyzed by 2-dimensional gel electrophoresis. The strain-specific Hb of DBA/2 mice (the line from which the Friend cells were derived by viral transformation) were synthesized in both the uninduced and the induced cells but at apparently markedly different rates. A monospecific antibody preparation against purified DBA/2 mouse .alpha.- and .beta.-globins was used to quantify the amount of these proteins in Friend cells during the course of dimethylsulfoxide-induced differentiation. Rocket gel immunoelectrophoresis, radial immunodiffusion analysis and competitive radioimmunoassay revealed that the uninduced Friend cells contained, on the average, about 0.45 pg of Hb/cell and this amount increased about 32-fold (to about 14.4 pg/cell) after 5 days of induction. The antibody preparation in indirect immunofluorescence studies revealed the constitutive synthesis of low levels of globins in virtually all of the uninduced, actively dividing, leukemia cells. The standardly used benzidine staining method for detecting Hb apparently is insensitive for the detection of low levels of these proteins. The cells in this particular leukemic population are already differentiated. The cells may represent an intermediate stage of erythroid maturation whose further progress along the normal in vivo terminal differentiation pathway is blocked by viral transformation. Perhaps various inducers, such as dimethylsulfoxide, may enable

关键词：联苯胺类细胞分裂细胞系细胞转化病毒克隆细胞/代谢二甲亚砜/药理学荧光抗体技术弗林德鼠白血病病毒珠蛋白类/生物合成血红蛋白类/分析免疫扩散白血病幼红细胞急性/代谢白血病实验性/代谢动物小鼠

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INHIBITION OF PEPTIDE CHAIN INITIATION BY A NONHEMIN-REGULATED TRANSLATIONAL REPRESSOR FROM FRIEND LEUKEMIA-CELLS

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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 1975年第1期171卷 145-153页

作者： CIMADEVILLA, JM KRAMER, G PINPHANICHAKARN, P KONECKI, D HARDESTY, B UNIV TEXAS CLAYTON FDNBIOCHEM INSTAUSTINTX 78712 UNIV TEXAS DEPT CHEMAUSTINTX 78712

A nonhemin-regulated translational repressor protein has been purified partially from the postribosomal supernatant fraction of Friend leukemia cells grown in the absence of dimethylsulfoxide. This repressor inhibits protein synthesis in lysates from rabbit reticulocytes or Friend leukemia cells and in a fractionated system using Artemia salina ribosomes, reticulocyte mRNA, and soluble components from reticulocytes. In contrast, the hemin-controlled repressor from reticulocytes does not inhibit protein synthesis in lysates from Friend leukemia cells. The repressor from Friend leukemia cells has no effect on poly(U)-directed synthesis of polyphenylalanine using reticulocyte ribosomes nor on the extension and release of nascent globin chains that were initiated in intact reticulocytes. It does not block completion of peptides on ribosomes isolated from reticulocytes incubated with NaF nor does it inhibit initiation factor-dependent formation of methionylpuromycin, but it inhibits globin mRNA-dependent methionylvaline synthesis. The Friend leukemia cell repressor promotes peptide synthesis-dependent breakdown of polysomes in reticulocyte lysates that appears to involve inhibition of ribosome reattachment to mRNA during peptide chain initiation. It is concluded that the Friend leukemia cell repressor blocks peptide initiation at a point between the addition of methionyl-tRNAfMet to the ribosomal initiation complex and the NaF-sensitive reaction.

关键词：弗林德鼠白血病病毒氯化血红素/药理学白血病实验性/代谢肿瘤蛋白质类/生物合成肿瘤蛋白质类/药理学肽链延伸翻译/药物作用肽链起始翻译/药物作用肽链终止翻译/药物作用嘌呤霉素/代谢 RNA 信使/代谢网状细胞/药物作用网状细胞/代谢核糖体/药物作用核糖体/代谢动物兔

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LYMPHOCYTE SURFACE RECEPTORS AND LEUKEMIA VIRUS-INDUCED IMMUNOSUPPRESSION

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AMERICAN JOURNAL OF CLINICAL PATHOLOGY 1975年第5期63卷 735-747页

作者： FRIEDMAN, H KATELEY, JR ALBERT EINSTEIN MED CTR DEPT MICROBIOLPHILADELPHIAPA 19141

The number and distribution patterns of lymphocytes in the spleens and lymph nodes of Balb/c mice which express immunoglobulin surface receptors were studied in terms of the effects of a murine leukemia virus on the immune-response mechanism. Friend leukemia virus induces a prompt, marked depression of the immune response of mice to antigens such as sheep erythrocytes and E. coli LPS. A functioning T- and B-lymphocyte system is necessary for the response to the SRBC's whereas E. coli LPS, a T cell-independent antigen, stimulates B cells alone. Although the responses to both classes of antigen were markedly depressed in FLV-infected mice, the major defect appeared to be impairment of B-cell function, at least early in the course of infection. In order to examine in more detail the mechanism of interaction between FLV and lymphoid cells with Ig surface receptors, presumably B cells, immmunofluorescent analyses were performed with spleen, and lymph node cells from FLV-infected mice. Within a few days after infection there was a marked decrease in the percentage of spleen cells with Ig surface molecules, although the absolute number of these cells was either unchanged or increased due to marked splenomegaly caused by the virus. A marked decrease in the percentage of splenocytes with theta antigen, considered a marker for mature T cells, also was evident in infected mice. The number of spleen cells showing evidence of FLV infection (i.e., positive for FLV-associated antigens) increased rapidly during the first few days after infection, and within 2 to 2 1/2 weeks nearly all of the nucleated splenocytes were positive for the tumor antigen. In contrast to the results for spleen cells, there were increases rather than decreases in the percentages of Ig-positive and theta-positive cells in the lymph nodes after infection. The number of lymph-node cells that showed the presence of FLV antigen was much lower than in the spleen, and their appearance was also much slower as the

关键词：抗体生成抗原病毒/分析 B淋巴细胞/免疫学 B淋巴细胞/超微结构细胞膜/免疫学红细胞/免疫学大肠杆菌/免疫学弗林德鼠白血病病毒免疫细胞免疫球蛋白类免疫抑制法白血病实验性/免疫学白血病实验性/病理学脂多糖类/免疫学淋巴结/病理学小鼠近交BALBC 受体药物绵羊/免疫学脾/病理学 T淋巴细胞/免疫学 T淋巴细胞/超微结构动物人类小鼠

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AFFERENT AND EFFERENT INTERFERENCE OF CELL-MEDIATED CYTOTOXIC REACTIONS BY HEPARIN

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 1976年第2期57卷 455-457页

作者： TING, CC NCI CELL BIOL LABBETHESDAMD 20014

Heparin influenced the induction (afferent interference) and effector (efferent interference) phases of cell-mediated cytotoxic reactions against FBL-3 cells, a syngeneic Friend virus-induced leukemia in inbred C57BL/6 mice. Heparin was cytotoxic at high concentrations (greater than or equal to 100 U/ml) and inhibitory for cell-mediated cytotoxic response at lower concentrations (less than or equal to 50 U/ml).

关键词：细胞毒性试验免疫弗林德鼠白血病病毒肝素/药理学免疫细胞/药物作用白血病实验性/免疫学小鼠近交C57BL 动物小鼠

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INVIVO DISTINCTION BETWEEN A TARGET-CELL FOR FRIEND VIRUS (FV-P) AND MURINE HEMATOPOIETIC STEM-CELLS

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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 1976年第2期57卷 443-445页

作者： NASRALLAH, AG MCGARRY, MP SUNY BUFFALO ROSWELL PK DIV DEPT PHYSIOL BUFFALO NY 14263 USA NEW YORK STATE DEPT HLTH ROSWELL PK MEM INST DEPT BIOL RESOURCES BUFFALO NY 14263 USA

Busulfan (BU) treatment of DBA/2 mice with hypertransfusion (HT)-induced polycythemia resulted in an ablation of detectable hematopoietic stem cells (CFUS) in pooled marrow from the long bones. Daily injections of erythropoietin (EP) stimulated an EP-responsive population of cells in the absence of detectable CFUS. Mice treated with BU and EP and having HT-induced polycythemia were inoculated with the polycythemia inducing strain of Friend virus (FVP) and determinations were made for the presence of tumor colony-forming units (tCFU). No change in CFUS/106 bone marrow cells was detected as a result of EP treatment. tCFU were increased more than 100 fold in HT-BU-EP-treated mice compared with saline-treated controls. The demonstration of tCFU in mice in which CFUS were not detectable indicated that this leukemogenic effect of FVP could occur in the absence of the pluripotent stem cell. The increased numbers of this FVP target cell in EP-stimulated, BU-treated mice with HT-induced polycythemia supported the model locating the target for this effect in the EP-responsive cell population.

关键词：白消安/药理学细胞转化肿瘤红细胞/微生物学红细胞生成素/药理学弗林德鼠白血病病毒造血干细胞/药物作用造血干细胞/微生物学小鼠近交DBA 红细胞增多症/病理学动物女(雌)性小鼠

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DISCUSSION PAPER - PROTECTIVE IMMUNITY IN LEUKEMIC MICE TREATED WITH SPECIFIC IMMUNOGENIC RNA

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP20期277卷 708-715页

作者： FRIEDMAN, H ALBERT EINSTEIN MED CTR DEPT MICROBIOL PHILADELPHIA PA 19141 USA

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.

关键词：抗原肿瘤弗林德鼠白血病病毒免疫法被动白血病实验性/免疫学白血病实验性/微生物学白血病实验性/治疗小鼠近交BALBC RNA/免疫学 RNA/治疗应用脾/免疫学脾/病理学脾大/病因学脾大/微生物学动物男(雄)性小鼠

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BUDR INHIBITION OF POST-DMSO-INDUCED ERYTHROLEUKEMIA CELL-DIFFERENTIATION INVITRO

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BRITISH JOURNAL OF CANCER 1976年第5期33卷 561-563页

作者： PREISLER, HD ROSWELL PK MEM INST DEPT MED A BUFFALO NY 14263 USA

The addition of BUdR [bromodeoxyuridine] to secondary cultures of control or DMSO [dimethylsulfoxide] treated mouse Friend leukemia cells had no effect on cell growth during the 3 day secondary culture period. The amount of heme synthesized per cell and the proportion of benzidine positive cells was decreased in each instance by .apprx. 50%. It seems surprising that the increment in the amount of heme/106 cells during secondary culture appeared to be less than the increment in heme per culture. This observation arises because the rate of increase in differentiated cells during secondary culture was less than the rate of increase in undifferentiated cells in the same culture. The proportion of differentiated cells in the secondary culture actually declined. These leukemic cells continue to synthesize and accumulate globin mRNA after removal of DMSO from the culture medium, and interference with this process inhibits differentiation during secondary culture in DMSO free medium.

关键词：溴脱氧尿苷/药理学细胞分化/药物作用细胞培养的二甲亚砜/药理学弗林德鼠白血病病毒白血病幼红细胞急性/化学诱导白血病幼红细胞急性/病理学白血病实验性/病理学动物

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