Proliferation in murine epidermis after minor mechanical stimulation. Part 2. Alterations in keratinocyte cell cycle fluxes.

We have recently shown that a mild mechanical irritation (tape strip) of the epidermis on the back skin of adult mice induces a strong and long lasting increase in proliferative activity and cell production. This was revealed by following the fate of 3HTdR-pulse labelled cells within the basal and suprabasal layers. To obtain further insight into the dynamics of cell kinetic changes we also performed double labelling experiments with 3HTdR and BrdUrd at various times after tape stripping. The technique for analysing the data had to account for a non stationary cell flux. A novel biometrical technique was developed which provides parameter estimates on the S-phase duration, the cell cycle duration and a parameter characterizing the degree of nonstationarity. When applied to the mechanically irritated epidermis we observed that the cell flux through the S-phase in the basal layer was accelerated by a factor of 10 between 18 and 36 h post tape strip. This activation declined slightly in the subsequent days and remained 4-6 fold higher than in the normal steady state for over 7 days post tape strip. The duration of the S-phase was 3-5 h and showed little variation. We conclude that mild mechanical irritation only affecting the stratum corneum has major stimulatory effects on the cell kinetics of proliferative keratinocytes in the basal layer of the epidermis indicating the existence of a powerful regulatory mechanism.