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W Den Otter

Publications and source records attributed to W Den Otter.

At least 127 records · Page 7Linked to original sources
PubMed1985

Macrophage-like tumor cells as tools to study chemoattractive activity.

Macrophage-like tumor cells can be obtained in large quantities as rather homogeneous populations, making these cells useful for chemotaxis assays. Therefore, macrophage-like cells J774A, WEHI-3, P388D1, IC-21, and NCTC 1469, all of murine origin, and U937 of human origin, were tested for chemotactic activity to a number of chemoattractive agents, such as casein, an N-formyl tetrapeptide (N-formyl-L-norleucyl-L-leucyl-L-phenylalanyl-L-tyrosine), and culture supernatants of murine SL2 lymphoma cells. J774A and WEHI-3 macrophage-like cells of murine (BALB/c) origin expressed the strongest chemotactic activity to casein and N-formyl tetrapeptide, respectively. The results show that: very standardized chemotaxis assays can be performed using these cell lines; these assays require appropriate cell line-stimulus combinations; there are substantial differences among cell lines as to sensitivity to various chemoattractive substances; macrophage cell lines and functional mutants may be helpful for the study of receptors for chemotaxins and the study of transducer signals for chemotaxis.

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PubMed1985

Tumor cells do not arise frequently.

A hypothesis greatly influencing thinking and experimental work in tumor immunology is that many tumor cells arise daily in an organism. However, relatively low numbers of tumours become clinically manifest. This discrepancy has initially led to the hypothesis that the great majority of these potential tumors is killed by immune surveillance mechanisms. After some time, however, serious objections were raised against this function of the immune system. When the interest in immune surveillance faded away, investigators started to study natural resistance against the de novo arising tumor cells. In this paper the data on natural resistance (and immune surveillance) are reviewed. These data lead to the conclusion than an efficient natural resistance that could kill many de novo arising tumor cells is lacking. Taken together the data suggest that no tumors arise when immune surveillance and/or natural resistance are absent. This implies that tumor cells probably do not arise frequently. Acceptance of this conclusion leads to a reappraisal of the role of immune surveillance and natural resistance against tumor cells. This reappraisal will mean a shift from the hypothesized failsafe mechanisms to mechanisms that may or may not kill rarely arising tumor cells, depending for instance on the antigenicity of the tumor cells and their sensitivity to tumoricidal mechanisms.

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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.

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PubMed1985

A role for mast cells and the vasoactive amine serotonin in T cell-dependent immunity to tumors.

The involvement of mast cells in anti-tumor resistance was studied by employing 2 strains of mast cell deficient but otherwise immunocompetent mice on a C57BL/6 (H-2b) background (W/Wv and Sl/Sld) and their respective normal +/+ littermate controls. Sensitization of control mice with irradiated semisyngeneic B16 melanoma cells (H-2b) resulted in protection against subsequent challenge with viable B16 cells, in contrast to sensitization of either W/Wv or Sl/Sld mice. The involvement of serotonin in antitumor resistance was studied by employing 2 serotonin active drugs: reserpine, that depletes mast cells of serotonin; and methysergide, a serotonin antagonist. Sensitization of BDF1 mice with irradiated B16 cells and sensitization of DBA/2 mice (H-2d) with irradiated SL2 cells (H-2d) resulted in protection against subsequent challenge with viable B16 cells and viable SL2 cells, respectively. Treatment with either reserpine or methysergide resulted in a decreased protection. Delayed-type hypersensitivity (DTH) footpad responses to allogeneic L5178Y (H-2d) tumor cells in C57BL/6 mice showed a biphasic reaction pattern, similar to that found in DTH responses to simple reactive haptens, such as picryl chloride. Moreover, the early swelling responses were also dependent on T cells and on mast cells. BDF1 mice carrying a semisyngeneic L5178Y tumor on the chest showed an early swelling response after footpad challenge but no late response, possibly indicating that selective down regulation of the late component of DTH was associated with progressive tumor growth in these animals. The biphasic patterns of DTH to both tumor cells and picryl chloride and the T cell and mast cell dependence of both antitumor resistance and DTH to tumor cells suggest that T cell-dependent activation of mast cells to allow entry of mononuclear leukocytes into sites of tumor growth is similar to the mechanism that occurs in DTH.

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PubMed1984

Specific localization of In-111-labeled monoclonal antibody versus 67-Ga-labeled immunoglobulin in mice bearing human breast carcinoma xenografts.

A murine monoclonal antibody reacting with more than 95% of all breast cancers was radiolabeled with In-111 and injected IP into nude mice bearing human breast carcinoma xenografts, together with Ga-67-labeled normal mouse immunoglobulin. Images were produced with a gamma camera in dual isotope mode. Tumors could be localized clearly with In-111-labeled specific monoclonal antibody, but improved visualization was obtained after computer-assisted subtraction of the image with Ga-67-labeled nonspecific immunoglobulin. The tumor-to-tissue contrast was improved from 2.3 to 5.9 after subtraction. Imaging with In-111-radiolabeled monoclonal antibody was superior to imaging with iodinated antibody. For the first time it was shown that images of two chemically related isotopes, Ga-67 and In-111, coupled to nonspecific and specific antibody, respectively, and simultaneously injected, can be subtracted to show the preferential uptake of the specific antibody in the tumor. As these isotopes are routinely used in clinical practice this technique may prove to be more practical for immunodetection of tumors in patients than existing imaging techniques.

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PubMed1984

Lymphocyte-induced macrophage cytotoxicity. Production of specific macrophage arming factor by sensitized Lyt 1+2+ T-lymphocytes.

T cells obtained from C57BL (H-2b) mice, that were immunized against allogeneic SL2 (H-2d) tumor cells, were able to produce a factor with the capacity to render macrophages cytotoxic. The factor producing T cells were of the Lyt 1+2+ phenotype. The factor was only produced by the T cells after triggering in vitro by SL2 cells or other cells with H-2d antigens. The macrophages armed with the factor only killed tumor cells with H-2d antigens. The factor was absorbed from the supernatant by macrophages and by cells bearing H-2d antigens but not by other cells. This showed that the factor has an affinity for macrophages and the specific sensitizing alloantigen. Therefore, the specificity of the lymphocytes is the same as the specificity of the factor and the factor-armed macrophages. The factor produced by the Lyt 1+2+ T cells is therefore the specific macrophage arming factor.

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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.

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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.

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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.

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PubMed1983

Macrophage-like cell lines: endogenous peroxidatic activity, cell surface antigens, and colony-stimulating factor production.

The murine macrophage-like cells NCTC 1469, J774A, WEHI-3, IC21, and P388D1, were compared with respect to their peroxidatic activity, display of cell surface antigens, and production of colony-stimulating factor. Peroxidatic activity was demonstrated in the nuclear envelope and in the cisternae of the rough endoplasmic reticulum of NCTC 1469 cells, J774A cells, and P388D1 cells, and in granules of WEHI-3 cells and IC21 cells. Colony-stimulating factor was produced only by WEHI-3 cells. NCTC 1469 and IC21 cells had a weak expression of M1/69 and Mac-1 antigens, whereas P388D1 cells expressed these antigens at a high level. WEHI-3 cells expressed M1/69 at a high level and Mac-1 at a low level, whereas J774A cells had an opposite expression T 200, Pgp-1, and ThB antigens were expressed at different levels by the various cell lines, without overt correlation among themselves or with the expression of M1/69 or Mac-1 antigens. These data suggest that macrophage-like cell lines cannot be placed in a maturation/differentiation lineage.

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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.

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