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H F Dullens

Publications and source records attributed to H F Dullens.

At least 55 records · Page 3Linked to original sources
PubMed1986

Specific tumoricidal activity of cytotoxic macrophages and cytotoxic lymphocytes.

The antitumor potency and specificity of syngeneic immune peritoneal exudate cells were tested. Groups of DBA/2 mice were immunized against syngeneic SL2 tumor cells. Then 6 days after the last immunization the antitumor potency, and the specificity of the immunization reaction was tested by injecting groups of the immunized mice with 10(3) to 5 X 10(7) DBA/2 derived L1210, L5178Y, P815 or SL2 tumor cells, and injecting immune peritoneal exudate cells into DBA/2 mice which had been injected 2 h earlier i.p. with 2 X 10(4) or 2 X 10(5) L1210, L5178Y, P815, or SL2 cells. Furthermore the tumor specific cytotoxicity in vitro of isolated immune (vs SL2) peritoneal macrophages was tested against L1210, L5178Y, P815, and SL2 cells. The "reciprocal" experiments (previous immunization against L1210, L5178Y, or P815 cells and 'challenge' with SL2) were also done. Finally, we tested the tumor-specific cytotoxicity of isolated immune peritoneal T-lymphocytes. It was shown that the rejection of tumor cells in previously immunized mice, the antitumor efficacy of the transferred immune peritoneal exudate cells and the in vitro cytotoxicity of purified immune peritoneal macrophages and lymphocytes, were tumor-specific reactions. That is only between the SL2 and L5178Y tumors were cross-reactions observed. However, this cross-reaction was not found at the level of cytotoxic T-cells. This suggests that cytotoxic T-cells and cytotoxic macrophages probably have different mechanisms of recognition of the specific tumor target cells. Treatment of macrophage monolayers, prepared from macrophages of immunized mice, with monoclonal anti-Thy-1 antibodies plus complement caused no decrease in cytotoxicity. This shows that macrophages can really express specific cytotoxicity. Tumoricidal macrophages probably obtain their tumor specificity through the activities of tumor-specific factors produced by sensitized T-cells.

Animals↗
PubMed1986

The role of host lymphocytes and host macrophages in antitumor reactions after injection of sensitized lymphocytes and tumor target cells into naive mice.

DBA/2 mice were immunized i.p. against syngeneic SL2 lymphosarcoma cells. At various days after the last immunization peritoneal and spleen lymphocytes were collected. The lymphocyte suspensions were enriched for T-cells by nylon wool filtration. The peritoneal T-cells from immunized mice (a) expressed direct specific antitumor cytotoxicity in vitro, (b) induced macrophage cytotoxicity in vitro, and (c) exerted tumor neutralization measured in a Winn-type assay. Spleen T-cells from these immunized mice (a) expressed no direct specific antitumor cytotoxicity in vitro, (b) only induced moderate macrophage cytotoxicity in vitro, but (c) exerted tumor neutralization in a Winn assay. For effective tumor neutralization in vivo effector target cell ratios of 1000:1 were required. When the effector/target ratio of 1000:1 was maintained but the absolute numbers of effector and target cells were lowered from 10(6) to 10(5) lymphocytes and 10(3) to 10(2) target cells respectively, no tumor neutralization was obtained. The major effect of the sensitized-transferred T-lymphocytes seemed to be the induction of cytotoxic macrophages in the (naive) recipient mice, as the peritoneal macrophages collected from the recipient mice 7 days after i.p. injection of a mixture of sensitized T-cells and tumor cells were cytotoxic. Purified peritoneal T-lymphocytes collected from these recipient mice were able to induce macrophage cytotoxicity in vitro but expressed no cytotoxic T-cell activity. In conclusion, our results show that in the tumor system used, tumor neutralization after transfer of sensitized lymphocytes is not dependent on the presence of cytotoxic T-lymphocytes. Lymphocytes with the strongest potency to render macrophages cytotoxic (in vitro and in vivo) also induce the best tumor neutralization in vivo, suggesting an important role for host macrophages as antitumor effector cells.

Animals↗
PubMed1986

A survey of some formal models in tumor immunology.

Computer technology has acquired an important role in structuring a variety of biological systems. The availability of modern powerful computers has stimulated the development of good and accurate models of biological systems. Biological systems, such as the immune response against cancer, are complex and it is difficult to experimentally control all the interacting elements constituting the immune response of a host to cancer. Complex biosystems do not always behave or act as expected during experimental investigation. In these cases computer models can be helpful in understanding the behavior of such complex systems. The purpose of this review is to consider the use of mathematical models to study the immune response against cancer. The logic and design of some operable models relevant for tumor immunology will be discussed. Special attention is given to the conceptualization of a model based upon a new hypothesis of tumor rejection presented by De Weger et al. [10]. Technical details concerning the mathematical aspects, differential equations, details on hardware and software package etc. are not included in this survey. These details are contained to in the original papers.

Computer Simulation↗
PubMed1986

Higher ADCC of murine peritoneal cells after immunization with allogenic tumor cells as compared with stimulation by adriamycin, BCG, and thioglycolate.

Normal peritoneal cells or spleen cells from C57BL mice could not lyse SRBC in an ADCC assay. After intraperitoneal injection of Adriamycin, BCG or thioglycolate the ADCC of peritoneal cells toward antibody-coated SRBC was elevated to 30% in contrast to the ADCC of spleen cells. However, peritoneal cells but not spleen cells of mice immunized with allogenic tumor cells (DBA SL2) showed ADCC levels at least two times higher than the levels observed after stimulation by other agents. Maximal ADCC levels (55.8%) were observed 10 to 15 days after immunization. Direct cytotoxicity towards SRBC increased to a maximum of 17.7% at 9 days after immunization. The effector cells in this system are thought to be macrophages, for ADCC activity was only present in the plastic-adherent cell fraction. Cell to cell contact was necessary for ADCC to occur; nonsensitized erythrocytes were not lysed when added to a mixture of effector cells and sensitized erythrocytes. Concentrations of antibody of 1 pg/ml were sufficient to induce ADCC, and effector cell to target cell ratios could be as low as 0.05. The finding that macrophages of mice immunized with allogenic tumor cells exhibit higher ADCC levels than macrophages elicited in other ways can contribute to the investigation of combined cancer therapy with antibodies and biological response modifiers.

Animals↗
PubMed1985

Antibacterial resistance, macrophage influx, and activation induced by bacterial rRNA with dimethyldioctadecylammonium bromide.

Intraperitoneally injected rRNA from Pseudomonas aeruginosa combined with dimethyldioctadecylammonium bromide (DDA) increased nonspecifically the resistance of mice against an intraperitoneal challenge with extracellular (P. aeruginosa, Escherichia coli) and intracellular (Listeria monocytogenes) bacteria. This study concerns the mechanism underlying the nonspecific resistance. RNA with DDA (RNA-DDA) induced a cell influx and activated peritoneal macrophages (M phi) as judged by the decreased 5'-nucleotidase and alkaline phosphodiesterase activities in M phi lysates, the enhanced O2- release, and the increased antitumor activity in comparison with unstimulated M phi. RNA without DDA did not enhance the resistance and did not influence the peritoneal cell numbers or M phi properties. DDA without RNA enhanced the resistance of mice only slightly; it induced a cell influx, yielding elicited M phi as judged by the decreased 5'-nucleotidase activity and increased alkaline phosphodiesterase activity, the slightly enhanced O2- release, and the absence of increased antitumor activity. Both RNA-DDA and DDA M phi showed an enhanced capacity to ingest and kill L. monocytogenes in vitro, DDA M phi being slightly less effective than RNA-DDA M phi with respect to killing. We conclude that the enhanced killing capacity of M phi for L. monocytogenes is characteristic of both elicited DDA M phi and activated RNA-DDA M phi. The relationship between nonspecific resistance, peritoneal cell numbers, and antibacterial M phi activity is discussed. In addition, it is shown that RNA and DDA retain their activity when they are injected apart, suggesting that they activate M phi by sequential action.

5'-Nucleotidase↗
PubMed1985

Macrophage T lymphocyte interactions in the anti-tumor immune response: a mathematical model.

In this paper we present a model of the macrophage T lymphocyte interactions that generate an anti-tumor immune response. The model specifies i) induction of cytotoxic T lymphocytes, ii) antigen presentation by macrophages, which leads to iii) activation of helper T cells, and iv) production of lymphoid factors, which induce a) cytotoxic macrophages, b) T lymphocyte proliferation, and c) an inflammation reaction. Tumor escape mechanisms (suppression, antigenic heterogeneity) have been deliberately omitted from the model. This research combines hitherto unrelated or even contradictory data within the range of behavior of one model. In the model behavior, helper T cells play a crucial role: Tumors that differ minimally in antigenicity (i.e., helper reactivity) can differ markedly in rejectability. Immunization yields protection against tumor doses that would otherwise be lethal, because it increases the number of helper T cells. The magnitude of the cytotoxic effector cell response depends on the time at which helper T cells become activated: early helper activity steeply increases the magnitude of the immune response. The type of cytotoxic effector cells that eradicates the tumor depends on tumor antigenicity: lowly antigenic tumors are attacked mainly by macrophages, whereas large highly antigenic tumors can be eradicated by cytotoxic T lymphocytes only.

Animals↗
PubMed1983

An improved method of unit gravity sedimentation separation for murine peritoneal macrophage populations.

A new method for the separation of murine peritoneal macrophage populations is described. Different macrophage populations were separated by velocity sedimentation in a Percoll gradient. The macrophages were separated by size as was shown by a morphometrical analysis. The different macrophage populations differed in their enzyme cytochemical profile. The overall recovery of peritoneal cells is more than 95% and the macrophages adhered normally to glass surfaces after washing. This indicated that this l X g sedimentation separation of macrophages, which is relatively simple to perform, is suitable for the study of macrophage heterogeneity.

Animals↗
PubMed1983

Eradication of tumor cells after injection into immunized hosts compared with the eradication of tumor cells after transfer of immune peritoneal exudates into tumor-bearing recipients.

DBA/2 mice were immunized against the syngeneic SL2 lymphoma by two or five injections with irradiated lymphoma cells given IP or SC, respectively. The antitumor efficacy induced in immunized mice was tested by (a) IP injection of the immunized mice with nonirradiated tumor cells and (b) transfer of the total 'immune' peritoneal exudate, the cellular fraction only, or the cell-free fraction only, IP into tumor-bearing recipients, or (c) tumor neutralization tests (Winn assay). It was shown that immunized mice were able to reject 5 X 10(7) SL2 tumor cells (8 of 14 mice survived greater than 100 days), while in most transfer experiments 2 X 10(5) SL2 cells could be eradicated. In the tumor neutralization experiments a number of 10(6) SL2 cells were eradicated. When the immune exudates were given before the inoculations of SL2 tumor cells the number of survivors increased significantly. Further, it was shown that the cellular fraction is the major contributor to the antitumor effect in the transfer experiments, since there was no significant difference in tumor eradication after injection of a complete immune exudate and after injection of the isolated cellular fraction. Injection of the noncellular fraction had no measurable antitumor effect. An increase in the number of injections with total peritoneal exudates from immunized mice did not result in an increase in tumor eradication in the tumor-bearing recipients. Extra stimulation (IP) of immunized mice with 10(4) nonirradiated cells 6 days after the last immunization resulted in an increase of the antitumor efficacy of these peritoneal exudates of these mice when collected 4-24 h after this stimulation. Extra stimulation with 10(6) irradiated cells had no measurable effect.

Animals↗
PubMed1983

The use of P815: a warning.

It is generally known that many malignancies are accompanied by forms of impairment of the immune system of the host. Also P815 mastocytoma cells can exert suppressive effects on the immune response reaction in vivo and in vitro. However, we have found a product released by P815 cells, which is able to activate macrophages non-specifically; macrophages normally not cytotoxic against tumor cells become cytotoxic against various tumor cell lines upon incubation with the P815 product. Nevertheless the same product which induces macrophage activation in vitro, seems to cause enhancement of tumor growth in vivo. We feel, if the activity of a tumor product depends so strongly on the experimental conditions used, one should be very careful in interpreting the results of experiments in which P815 cells are used as target cells.

Animals↗
PubMed1982

Cell surface antigen phenotypes and enzyme expression patterns of two murine T-cell lymphomas derived from early and/or mature thymus cells.

A number of cell surface markers (T200, ThB, Thy1, Lyt1 and Lyt2 and a glycolipid) and enzymes (ATP-ase, acid phosphatase, beta-glucuronidase, 5'-nucleotidase, non-specific esterase, ANAE and chloroacetate esterase) were determined for two murine T-cell lymphomas: the DBA/2-strain-derived SL2 with a phenotype close to that of a mature thymocyte and the GRS-strain-derived GSRL13 with a phenotype of a more primitive thymocyte. While the pattern of expression of the enzymes was similar for SL2 and GRSL13 and as such indistinguishable from that of the majority of thymus cells, the pattern of cell surface antigen expression was clearly different. GRSL12 cells express the ThB antigen and a glycolipid antigen detectable with monoclonal antibody 30-H11, but not Lyt1 and Lyt2 antigens. SL2 cells, however, do not express ThB and the glycolipid antigen, but do express Lyt1 and Lyt2.

Animals↗
PubMed1982

Staging, growth properties and metastatic behaviour of a transplantable murine T-cell lymphoma.

Cell surface markers, enzymatic patterns, proliferation characteristics and metastatic behaviour of the DSA/2 derived SL2 lymphoma were determined. SL2 cells are sensitive to a heterologous antiserum to murine T-cells and to allo-antisera for Thy 1.2 and TL 1.2.3. They show acid-phosphatase, betaglucuronidase, acid-alpha-naphthytesterase and non-specific esterase staining. The reactions for ATP-ase, and 5'nucleotidase were negative. The SL2 tumour cells can be transplanted in vivo, growing rapidly both as an ascites or a solid tumour, and can be grown in vitro as a suspension culture (doubling time about 18 hours). One hundred cells kill an animal after i.p. transplantation, while 1,000 cells kill an animal after s.c. transplantation. Histopathological examination combined with TEM shows that SL2 metastasizes rapidly, especially after i.p. injection. The metastasizing cells reach the blood vessels in the lung septa and extravascular positions in the liver.

Animals↗
PubMed1982

Peritoneal cell populations during tumour injection.

The response of peritoneal cells to the SL2 lymphoma was studied in immunized and non-immunized mice to elucidate further the cellular events that lead to tumour rejection in an allogeneic and a syngeneic tumour system. Anti-tumor immunity was induced by intraperitoneal injection of normal, irradiated or mitomycin-C treated tumour cells. Four different immunization schedules were tested. The response of the peritoneal cells was investigated by studying the peritoneal cell population kinetics (appearance and/or disappearance of various cell types e.g. mononuclear phagocytes, lymphocytes, PMNS and mast cells). Total cell counts were done using phase contrast microscopy, differential cell counts were done on cytocentrifuge slides, stained with May Grünwald-Giemsa. The activity of the lysosomal enzyme beta-glucuronidase present in mononuclear phagocytes was also studied. The results indicated that the composition and morphology of the cellular fraction of the peritoneal exudate changes quite dramatically during tumour rejection. Especially the beta-glucuronidase activity of the mononuclear phagocytes line varies significantly. The observed changes in the cellular population depended upon the dose of tumour cells injected i.p. No significant differences were observed between the peritoneal cell populations of mice grafted i.p. with irradiated or with mitomycin-C treated tumour cells. On the other hand when mice previously immunized with three injections with 10 irradiated or mitomycin-C treated tumour cells were challenged i.p. with various doses of tumour cells, the immune potency against the tumour is greater after previous immunization with irradiated SL2 cells than after immunization with mitomycin-C treated tumour cells.

Animals↗
PubMed1981

Murine macrophage cytotoxicity induced by mastocytoma cells, cell-free mastocytoma exudates, and extracts.

Peritoneal macrophages obtained from normal CBA mice expressed significant cytotoxicity against the DBA/2-derived P815 mastocytoma but not against DBA/2-derived SL2 tumor or the C57BL-derived tumors TLX9 and EL4. The macrophages also expressed some cytotoxicity against the DBA/2-derived L5178Y tumor. Incubation of normal CBA macrophages with cell-free exudate of intraperitoneally growing P815 cells resulted in cytotoxicity against the SL2 and against the EL4 lymphosarcoma. Incubation of SL2 tumor cells with P815 ascitic fluid before adding the SL2 tumor cells to normal CBA macrophage monolayers also resulted in inhibition of SL2 tumor cell growth on these monolayers. Trypsinization of the macrophages after incubation with ascitic fluid (or tumor extract) but before challenge with tumor cells abolished cytotoxic activity of the macrophages. Incubation of normal macrophages with a comparable amount of trypsin before tumor cells were added had no influence on their activity. Cytotoxicity could be induced after 7 days storage of the exudate at 5 degrees C, but this ability was lost within 72 hr when kept at room temperature. Storage at -20 degrees C had no influence. Gel fractionation of the cell-free exudate showed that the product responsible for the effect is a small molecular weight product (mol wt less than 1000). Furthermore the "product" was dialyzable. The "factor" could not be shown in the supernatant of P815 cell cultures unless the cultures comprised greater than or equal to 40% dead cells.

Animals↗
PubMed1981

A small molecular weight peptide from P815 mastocytoma cells induces macrophage cytotoxicity.

In a previous article we have shown the presence of a "factor" in the cell free exudates of intraperitoneally growing P815 mastocytoma cells as well as in cell-free tumor cell extracts. This "factor" is able to induce nonspecific macrophage cytotoxicity against tumor target cells. The "factor" was sensitive to heating at 100 degree C for 1 min, destroyed by pronase treatment, and dialyzable. On the other hand, the "factor" was not removed by centrifugation (25,000 x g), and was resistant to chloroform extraction, ultraviolet irradiation, heating at 56 degree C (for 20 min), or RNAase treatment. Sephadex gel fractionation of the mastocytoma exudate showed that the "factor" has an approximate molecular weight of 650-700 daltons. Normal peritoneal macrophages incubated with an extract of murine mast cells, purified histamine or serotonin did not show detectable cytotoxicity against tumor cells. The results of our experiments suggest that the effect of the P815 cell-free exudate and tumor cell extract is due to a dialyzable small molecular weight peptide.

Animals↗
PubMed1980

Oncostatic-antibody complexes in chemotherapy.

Cancer-chemotherapeutic agents are not selective in their action against cancer cells. An approach to increasing the efficacy of currently available antitumor drugs is the binding of selected chemotherapeutic agents to antibodies that do posses specific affinity for the tumor cells. In this short review consideration is given to some aspects of induction of antitumor antibodies, techniques for binding of various chemotherapeutic agents to antibodies, immunochemotherapy with oncostatic-antibody complexes and their mode of action, and future prospects of this form of therapy.

Animals↗