Interferon effects on microfilament organization, cellular fibronectin distribution, and cell motility in human fibroblasts

Abstract

We have shown previously (Pfeffer et al, 1979, Exp. Cell Res. 121:111-120) that treatment of human fibroblasts, planted at a density of 2 x 103 cells/cm2, with purified human fibroblast interferon (640 U/ml) for 3 d at 37 °C decreases the overall rate of cell proliferation to 35-40% of the control value. In the present experiments we have characterized the phenotype of interferon-inhibited fibroblasts. The mean volume of trypsinized, interferon-treated cells was increased 31% above that of control cells. The interferon-treated population was much more heterogeneous than the control population with respect to volume, and there was a considerable overlap in the volume distributions of the two populations. The cell surface area was, on the average, increased 65% after interferon treatment. More than 80% of the treated cells had enlarged nuclei, many of which were lobed, and the fraction of binucleated cells was increased fivefold. After interferon treatment, over 40% of the cells showed large actin-containing fibers in the form of multiple parallel arrays. Fewer than 5% of the control cells contained such large actin fibers. The number of actin fibers of all sizes was tripled in the treated fibroblasts on a per cell basis and, calculated per unit surface area of the cells, the number was increased 82%. In contrast, 10-nm filaments and microtubules did not appear to be increased in number per unit surface area of the cells. The increases per cell in the abundance of these structures were directly related to increased cell size. After interferon treatment, fibronectin was distributed in arrays of long filaments covering most portions of the cell surface. Interferon treatment markedly decreased the rate of cell locomotion as well as membrane ruffling and saltatory movements of intracellular granules. © 1980, Rockefeller University Press., All rights reserved.