Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro

In the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression.MMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms.Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been measured and found to be elevated in pleural exudates of different origin (parapneumonic, malignant, tuberculous). MMPs consist a family of proteolytic enzymes that break down virtually all the protein components of the extracellular matrix. The balance between matrix deposition and degradation is tightly regulated in human tissues and a disruption of this balance has been implicated in several pathological conditions such as cancer, cardiovascular diseases and arthritis [1,2]. MMP2 and MMP9 are thought to be involved in pleural fluid accumulation in the pleural cavity. The disruption of the integrity of the mesothelial layer or the underlying basement membrane, and therefore the facilitation of fluid influx into the pleural space has been proposed as a possible mechanism [3], although no study has been so far conducted.MMPs have been correlated with the induction of increased capillary permeability in several inflammatory conditions, such as brain and myocardium ischemia injury and diabetic retinopathy [4-6]. In in vitro studie