Receptor mediated activation of many cell types is followed by motility related events. In T lymphocytes, lateral redistribution of surface receptors is accompanied by aggregation of actin and myosin in cytoplasmic subcaps. Patching and capping of receptors after activation of lymphocytes from aged animals and humans is impaired, and it was inferred from indirect evidence that age-related changes in cytoskeletal functions are responsible. Concanavalin A activation of resting T lymphocytes resulted in actin polymerization in the cytoskeleton of cells from young but not aged C57BL/6 mice. Bypassing the plasma membrane to activate protein kinase C with PMA induced actin polymerization in resting T lymphocytes and in immunomagnetically isolated CD4 and CD8 positive subpopulations from young and aged mice, but the values were lower in cells from aged animals. Light microscopy visualization of the individual cells showed that following activation with PMA, the actin cytoskeleton reorganized and subcaps formed in CD4 and CD8 positive lymphocytes from both young and aged mice. However, in aged animals a significantly smaller percentage (30.5) of the cells exhibited cytoskeletal rearrangement compared to the percentage of cells from young mice (53.5), and the subcellular actin filament morphology differed from that of cells from young animals. The kinetics of the response to PMA did not differ in the two age groups. This suggests that although plasma membrane signalling events are bypassed and actin polymerization is initiated in cells from aged mice, actin filament function/s change with age and may depend on differences in actin binding protein and phospatidylinositol metabolism. This project will be terminated as the Principal Investigator has retired on June 30, 1995.
