MESOTHELIAL CELL RESPONSE TO PLEURAL INJURY - THROMBIN-INDUCED PROLIFERATION AND CHEMOTAXIS OF RAT PLEURAL MESOTHELIAL CELLS

Injury to the pleura ultimately results in either repair with fibrosis or repair without fibrosis and a re-establishment of the normal mesot helial monolayer. The role of the mesothelial cell, and of local media tors, in these repair processes remains essentially undefined. In orde r for repair without fibrosis to occur, mesothelial cells, in response to local mediators, must be capable of migration and/or proliferation to cover the injured and denuded mesothelium. We hypothesized that ra t pleural mesothelial cells were capable of both chemotaxis and prolif eration in response to thrombin. In an in vitro assay, mesothelial cel ls demonstrated directed migration in response to a known chemoattract ant, formylmethionylleucylphenylalanine. In addition, mesothelial cell s demonstrated chemotaxis in a dose-dependent manner in response to th rombin, with a maximal response at a concentration of 10(-8) M. Finall y, this chemotaxis was blocked by a specific blocker of thrombin, anti thrombin 3. Thrombin also stimulated mesothelial cell proliferation, w hich was measured both in a [H-3]thymidine incorporation assay and by direct cell counts. Again, the response was dose dependent, with the m aximal response at 10(-8) M causing the same amount of [H-3]thymidine incorporation as 10% fetal bovine serum. As before, this response was completely blocked by antithrombin 3. These results demonstrate that m esothelial cells are capable of both chemotaxis and proliferation in r esponse to thrombin. Thrombin may play an important role in the regula tion of pleural repair without fibrosis and the re-establishment of th e mesothelial monolayer.