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 reestablishment of the normal mesothelial monolayer. The role of the mesothelial cell, and of local mediators, in these repair processes remains essentially undefined. In order 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 rat pleural mesothelial cells were capable of both chemotaxis and proliferation in response to thrombin. In an in vitro assay, mesothelial cells demonstrated directed migration in response to a known chemoattractant, formylmethionylleucylphenylalanine. In addition, mesothelial cells demonstrated chemotaxis in a dose-dependent manner in response to thrombin, with a maximal response at a concentration of 10(-8) M. Finally, this chemotaxis was blocked by a specific blocker of thrombin, antithrombin 3. Thrombin also stimulated mesothelial cell proliferation, which was measured both in a [3H]thymidine incorporation assay and by direct cell counts. Again, the response was dose dependent, with the maximal response at 10(-8) M causing the same amount of [3H]thymidine incorporation as 10% fetal bovine serum. As before, this response was completely blocked by antithrombin 3. These results demonstrate that mesothelial cells are capable of both chemotaxis and proliferation in response to thrombin. Thrombin may play an important role in the regulation of pleural repair without fibrosis and the re-establishment of the mesothelial monolayer.
Hott
J W
JW
Department of Medicine, Veterans Administration Medical Center, Indianapolis, IN 46202.
Sparks
J A
JA
Godbey
S W
SW
Antony
V B
VB
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008168:Lung; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010994:Pleura / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D051381:Rats; D013917:Thrombin / Q000494:pharmacology*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D000990:Antithrombin III; D013917:Thrombin