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Biomedical subjects

E F Wheelock

Publications and source records attributed to E F Wheelock.

At least 55 records · Page 3Linked to original sources

Use of silica to identify host mechanisms involved in suppression of established Friend virus leukemia.

Silica, an agent predominantly toxic for macrophages, inoculated i.v. to Friend leukemia virus (FLV)-infected mice, blocks the FLV-leukemosuppressive effects of chlorite-oxidized oxyamylose (COAM)-statolon treatment. FLV-infected, COAM-statolon-treated mice that have received silica and have failed to suppress FLV leukemia produced normal amounts of interferon, but did not make antibodies cytotoxic for FLV leukemic cells. Transfer of untreated spleen cells, splenic T cells, or thymocytes from mice with suppressed FLV erythroleukemia to FLV-infected mice treated with silica and COAM-statolon restores the humoral immune response to FLV antigens and results in leukemosuppression. Thus, T lymphocytes from mice with suppressed erythroleukemia participate in FLV leukemosuppression either directly as effector cells, or indirectly as helper cell in the production of antibodies to FLV antigens.

Amylose↗

Suppression of extablished Friend virus leukemia by statolon: potentiation of statolon's leukemosuppressive activity by chlorite-oxidized oxyamylose.

Treatment of Friend virus (FV)-infected mice, 3 days after FV inoculation, with statolon, an extract of the mold Penicillium stoloniferum, induces interferon and restores immunocompetence to viral and nonviral antigens such as sheep erythrocytes. Clinical remissions are established in 20 to 70% of the infected mice. Cholorite-oxidized oxyamylose administered intraperitoneally 24 h before, 3 h before, or 3 h after statolon enhanced interferon production, but the increased number of mice protected against FV disease was more closely related to the associated enhanced synthesis of FV cytotoxic antibody. The prolonged selective immunodepression to intraperitoneal sheep erythrocytes after intraperitoneal administration of chlorite-oxidized oxyamylose-statolon appeared to be related to a stimulation in number and erythrocyte-phagocytic capacity of peritoneal macrophages. The marked activation of macrophages in FV leukemic mice after such treatment may also have contributed to the enhanced FV leukemosuppressive effects of chlorite-oxidized oxyamylose-statolon.

Amylose↗

Correlation of survival from murine cytomegalovirus infection with spleen cell responsiveness to Concanavallin A.

Spleen cells from nonlethally MCMV-infected weanling and adult DBA/2 mice had diminished responses to Con A stimulation. In contrast, only lethal MCMV infections were associated with a complete suppression of the Con A response. The immune response to SRBC was depressed even in asymptomatic infections of weanling and adult mice. A marked maturation of resistance to the lethal effects of MCMV infection was found to occur during the fourth week of life.

Age Factors↗

Depression of humoral immunity to sheep erythrocytes in vitro by Friend virus leukemic spleen cells: induction of resistance by statolon.

The in vitro antibody plaque-forming cell (PFC) response of normal spleen cells exposed to sheep erythrocytes in Marbrook chambers was depressed by the addition of Friend virus (FV) leukemic spleen cells. Fewer than 10-5 leukemic cells inhibited the PFC response of 10-7 normal cells. This immunodepression could not be produced with sonicated, irradiated, or mitomycin C-treated leukemic cells or with cellfree FV. It could be blocked by FV immune serum but was unaffected by high titers of purified interferon. Interferon did not inhibit the immune response of normal spleen cells to sheep erythrocytes. Spleen cells from mice treated with statolon or chlorite-oxidized oxyamylose statolon but not Newcastle disease virus or poly rI:poly rC were resistant to immunodepression in vitro by FV leukemic spleen cells. The unique ability of statolon to prevent immunodepression by leukemic spleen cells may be the basis of its FV leukemo-suppressive activity in vivo.

Animals↗

Impaired macrophage function in Friend virus leukemia: restoration by statolon.

Phagocytic and migratory functions of peritoneal macrophages from Friend virus (FV) leukemic mice are significantly depressed as compared with normal controls. Leukemic macrophages exposed in vivo and in vitro to statolon, an extract of the mold Penicillium stoloniferum, shown previously to suppress FV erythroleukemia, regain normal function and release reduced amounts of FV. Statolon's in vivo restoration of leukemic macrophage function is paralleled by restoration of humoral immune competence. Statolon induces interferon in vitro but its effects on leukemic macrophages are probably direct, since restoration of macrophage function occurs at dosage levels far below those that induce interferon. These studies suggest that macrophages play an integral role in both the pathogenesis and the statolon-induced suppression of FV disease.

Animals↗

Effects of intravenous silica on immune and non-immune functions of the murine host.

Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other that macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica.

Animals↗