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Biomedical subjects

R B Herberman

Publications and source records attributed to R B Herberman.

At least 19 recordsLinked to original sources
PubMed1979

Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity.

Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2-3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran-treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran-treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed.

Animals↗
PubMed1979

Augmentation of natural killer activity by pyran copolymer in mice.

Treatment of older mice with pyran copolymer, a known interferon-inducer, was found to result in a rapid boosting of cell-mediated cytolytic activity against YAC-1 tumor target cells. The effector cells were characterized as being non-adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in various lymphoid organs and was detectable 2-3 days after drug treatment. Differences in the levels of boosted activity among the lymphoid organs resulted when the route of administration was varied. The degree of augmentation was largely independent of the dose of pyran, but did vary among different strains of mice. Augmentation, moreover, was followed by a rapid decline by 5-7 days.

Adjuvants, Immunologic↗
PubMed1979

Immunochemical characterization of tumor-associated surface antigens on a Moloney leukemia virus-lymphoma, MBL-2.

Tumor-associated surface antigens (TASA) on a Moloney leukemia virus (M-MuLV)-induced lymphoma, MBL-2, in C57BL/6 mice (B6) were characterized. The surface proteins of MBL-2 cells were selectively radioiodinated and then extracted by Nonidet P40. The solubilized materials were then reacted with a variety of antisera: monospecific antisera to murine leukemia viral proteins (anti-gp69/71, anti-p30, anti-p15, anti-p12 and anti-p10), sera from B6 which regressed murine sarcoma tumors induced by murine sarcoma virus (anti-MSV) and a rabbit anti-MBL-2 antiserum. The resulting radioimmune precipitates were analyzed and compared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The following results were obtained. (1) Among all anti-viral protein antisera tested only anti-gp69/71 was active and detected a protein doublet of gp69/71 and its degradation fragments of 42,000 and 35,000 daltons. (2) Radioimmune precipitates prepared with anti-MSV showed a SDS-PAGE pattern similar to that seen with anti-gp69/71. This result indicated that the surface antigen detected by the anti-MSV serum on MBL-2 tumor cell was probably a viral envelope antigen. (3) The rabbit anti-MBL-2 serum detected on the cell membrane an antigen of approximately 95,000 daltons which was tumor-associated and did not appear to be related to virion components. The anti-MBL-2-serum still reacted with the 95,000 dalton antigen after absorption with disrupted M-MuLV virus and with gp69/71 and p30 purified from the virus.

Animals↗
PubMed1979

Suppression of lymphokine production by macrophages infiltrating murine virus-induced tumors.

Immune spleen cells from mice injected with murine sarcoma virus (MSV) can produce migration inhibition factor (MIF) in vitro after stimulation with intact tumor cells. We have now found that this effector function can be regulated by suppressor macrophages present in the tumor. The cells from the tumor (CfT) exert a strong suppressive effect even after treatment with anti-Thy 1.2 plus complement but lose this capacity if adherent or phagocytic cells are removed, suggesting that the macrophage is the suppressor cell. The effects of the suppressor cells were exerted on a proliferation-independent function of the lymphocytes, since MIF production, as well as its suppression, occurred even after proliferation of the lymphocytes was blocked by mitomycin-C. The implications of these findings are that macrophages can suppress some early events involved in the activation of lymphocytes by antigen and that they do so through a mechanism that does not relate to the proliferation of the cells.

Animals↗
PubMed1979

Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.

Animals↗
PubMed1979

Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts.

Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40-transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40-2303, 2931 and SV40-2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72-h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte-mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.

Adult↗
PubMed1979

Sensitive and convenient quantitation of antibody binding to cellular antigens using glutaraldehyde preserved cells.

As a preliminary step in the identification and isolation of antibodies to human cancers, we have developed a sensitive and convenient assay for antibody binding to cellular antigens. The basis for the method is antibody binding to glutaraldehyde-fixed cells (AbGfC) and quantitation with radioiodinated staphylococcal protein A (SpA). Glutaraldehyde fixation of intact cells, which does not appear to effect the ability to form antigen-antibody complexes, provides a convenient and standard supply of target cells which may be stored at 4 degrees C and used in the assay over a period of several months. The amount of antibody specifically bound to the cells is quantitated by the addition of 125I-labeled SpA. The sensitivity of the method was compared with two complement-dependent cytotoxicity methods (trypan blue exclusion and 51Cr release assays) and tested with two antisera to human lung cancer and one antiserum to a membrane antigen of a murine lymphoma. These comparisons indicated much greater sensitivity when compared with the trypan blue exclusion assay and equivalent sensitivity with greater dose response characteristics when compared with the 51Cr release assay.

Aldehydes↗
PubMed1979

Adriamycin-induced antitumor response in lethally irradiated mice.

Lethally irradiated mice pretreated with a wide range of Adriamycin (ADM) doses were tested for their in vivo antitumor response against transplanted lymphoma cells. Tumor growth, as assessed by 125IUdR uptake, was markedly impaired by treatment with ADM by a variety of different administration schedules. This ADM-induced antitumor response was largely dose-dependent, occurred regardless of route of administration, and was detectable as late as 15-30 days following drug treatment. No genetic restriction could be found to regulate the development of this response, since tumor growth inhibition occurred in syngeneic as well as allogeneic tumor-host combinations. ADM-induced antitumor response did not appear to be due to direct antitumor action by the drug, but rather to some interaction with host immune mechanisms. Antimacrophage agents, such as silica or carrageenan, abrogated the response. The possible implication of different cells as effectors of this response is discussed.

Animals↗
PubMed1979

The effect of immunopharmacological agents on mouse natural cell-mediated cytotoxicity and on its augmentation by poly I:C.

Treatment of young mice with lethal X-irradiation (900 R), cyclophosphamide, or hydrocortisone significantly depressed their spontaneous NK activity. The same treatments, however, did not inhibit the augmentation of NK function by poly I:C, suggesting the existence of a treatment resistant pre-NK cell. Both the spontaneous activity and its augmentation were readily inhibited by macrophage-toxic agents such as silica and carrageenan in vivo. Since the NK cells themselves were not macrophages, as shown by the inability of silica or carrageenan to block in vitro cytolysis of target cells, we postulated that macrophages were required to maintain NK activity in vivo and that they were essential accessory cells in the augmentation. The induction of interferon by poly I:C was also inhibited by silica and carrageenan. The augmentation of NK activity induced by poly I:C was consistently accompanied by the rise in serum IF levels of the treated mice, and its inhibition by the macrophage-toxic agents was followed by decreased production of interferon. These observations support our hypothesis that macrophages, in response to poly I:C, produced interferon which in turn activated NK cells to become cytolytic.

Animals↗
PubMed1979

Evidence for long-lasting tumor immunity in a syngeneic rat lymphoma model: correlation of in vitro findings with in vivo observations.

Previous studies concerning the tumor-host relationship in the (C58NT)D rat tumor system indicated that some T-lymphocyte responses against tumor antigens were only transiently detectable after tumor inoculation; however, more sensitive procedures for the detection of proliferative responses in the mixed lymphocyte-tumor interaction (MLTI ) have been developed. Upon reexamination of the kinetics of this response, positive responses were detected as long as 650 days after inoculation. Cytotoxic effector cells could be generated in MLTI with lymphocytes from immune WF rats as long as 1 year after inoculation, and evidence was provided which indicated that the persistence of the responses observed in vitro correlated well with the resistance of immune rats to rechallenge with (C58NT)D tumor cells in vivo.

AKR murine leukemia virus↗