Target-induced changes in macrophage migration may explain differences in lytic sensitivity among simian virus 40-transformed fibroblasts.

Abstract

Time-lapse video microscopy has been used to study macrophage movement in the presence of SV40-transformed fibroblasts. In all, five different SV40-transformed cell lines (an uncloned line and four clones derived from it) were tested for their affects on the movement of LPS-activated macrophages (AM). Conditions for video microscope recording were designed to simulate, as best as possible, the conditions used in a 51Cr-release cytotoxicity assay. Our analysis shows that these targets had a range of effects on macrophage migration, from stimulation to complete inhibition of movement. Two of the targets we tested (SV-COL and SV-COL-E8) both highly sensitive to lysis, stimulated macrophage movement, inducing an "agitated" response. Two other targets (SV-COL-F11 and SV-COL-H5), both of intermediate sensitivity had, for the most part, a suppressive effect on macrophage movement. Finally, we found that one target, clone SV-COL-F5, which is completely resistant to lysis by AM, was able to completely inhibit macrophage movement. This inhibitory effect was accompanied by a "pathologic" change in the structure of the macrophage cytoplasm suggesting that this target escapes lysis in vitro by secreting a factor that incapacitates the effector cell. Overall, these observations suggest that target cell products that can affect the behavior of the AM may be important in determining the lytic sensitivity of transformed target cells.