PLASMINOGEN ACTIVATORS ARE INVOLVED IN KERATINOCYTE AND FIBROBLAST MIGRATION IN WOUNDED CULTURES IN-VITRO

During skin repair both keratinocytes and fibroblasts migrate into the wounded area. In the process of cell migration, controlled proteolyti c degradation of the extracellular matrix occurs. It has been suggeste d that the plasminogen activator system is involved in such proteolyti c processes occurring during wound healing. The role of plasmin, uroki nase-type plasminogen activator (u-PA) and tissue-type plasminogen act ivator (t-PA) in keratinocyte and fibroblast migration in vitro was ex amined in the present study. Confluent cultures of normal human kerati nocytes, human squamous cell carcinoma (SCC-4), SV40 transformed kerat inocytes (SVK-14) and human fibroblasts were mechanically wounded and the repopulation of the denuded area was examined. Migration of cells into the denuded area could be inhibited by neutralizing antibodies ag ainst t-PA or u-PA, or the serine protease inhibitor Trasylol in all c ell types studied. For detailed study on involvement of u-PA and t-PA in migration processes wounded cultures of SVK14 cells were used. Both t-PA and u-PA activity could be detected at the migrating edge of SVK 14 cultures as revealed by zymography and by immunocytochemistry using polyclonal antibodies. Our results demonstrate the direct involvement of not only u-PA but also t-PA in migration of keratinocytes and fibr oblasts in wounded cultures in vitro.