Search PubMed⌕ Search

Biomedical subjects

R Keller

Publications and source records attributed to R Keller.

At least 397 records · Page 22Linked to original sources
PubMed1974

Modulation of cell proliferation by macrophages: a possible function apart from cytotoxic tumour rejection.

The in vitro interaction between activated, non-immune macrophages (AM) and a variety of syngeneic, allogeneic or xenogeneic "normal" and "malignant" target cell lines was followed by different parameters such as target cell proliferation, viability or morphology.Proliferation of all rapidly replicating cell lines examined, irrespective of whether they were of syngeneic, allogeneic or xenogeneic origin, or showed normal or neoplastic growth characteristics, was similarly blocked by the presence of AM in an effector/target cell ratio of 10:1. It was only in very slowly proliferating cells that this inhibitory effect was not detectable. A marked diminution in target cell proliferation was also achieved with target cells growing in suspension, where maintenance of close contact between effectors and targets is unlikely, indicating that this macrophage effect may be mediated by a soluble product of AM.The finding of clear differences in the proliferation inhibition of slowly proliferating normal and neoplastic targets suggested that proliferation per se may not fully mirror the consequences of the macrophage/target cell interaction. This was affirmed when viability and morphology were used as parameters: viability was virtually unaffected in normal targets whereas neoplastic cells were killed.Accordingly, it is suggested that activated non-immune macrophages can affect targets in strikingly different ways. Inhibition of proliferation could be an important homoeostatic regulatory function of the macrophage which would affect every replicating cell. Cytocidal killing of targets, on the other hand, is achieved only on neoplastic cells.

Animals↗
PubMed1973

Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages.

Syngeneic tumor cell lines induced in inbred DA rats by polyoma virus, dimethylbenzanthracene, or methylcholanthrene were interacted in vitro with syngeneic effector cells. Glycogen-induced peritoneal exudate cells, predominantly polymorphonuclear leukocytes, and proteose peptone-induced peritoneal cells, principally macrophages, were the effector cells employed. Activated, nonimmune macrophages or exudative polymorphonuclear leukocytes produced pronounced morphological changes in syngeneic tumor cells as evidenced by a substantial reduction in tumor cell numbers and appearance of shrunken cells, even though there was no increase in cell debris. Polymorphonuclear leukocytes exerted a generally similar but quantitatively much diminished effect. These effector cells constantly produced a decrease in the incorporation by tumor cells of DNA precursors such as [(3)H]thymidine and of RNA precursors such as [(3)H]uridine. In this regard, the effector cells were quite refractory to high doses of X-irradiation. Interaction of target cells with activated, nonimmune macrophages yielded low but consistent signs of cytotoxicity, whereas polymorphonuclear leukocytes gave no such effects. Elimination of functional macrophages by silica, an agent specifically toxic for macrophages, resulted in unrestricted tumor cell proliferation despite continued generation of cytotoxicity. Accordingly, cytostatic mechanisms appear to play a predominant role in the elimination of tumor cells by nonimmune phagocytes. Evidence from a variety of experimental approaches suggest that the cytostatic effect is dependent on cell-to-cell contact.

Animals↗