ROLE OF MESENCHYMAL CELL-DEATH IN LUNG REMODELING AFTER INJURY

Repair after acute lung injury requires elimination of granulation tis sue from the alveolar airspace. We hypothesized that during lung repai r, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, wo uld be present at the air-lung interface. Bronchoalveolar lavage fluid obtained from patients during lung repair induced both fibroblast and endothelial cell death, while fluid obtained at the time of injury or from patient controls did not. The mode of cell death for endothelial cells was apoptosis. Fibroblast death, while morphologically distinct from necrosis, also differed from typical apoptosis. Only proliferati ng cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination o f lung tissue from patients after lung injury revealed evidence of apo ptotic cells within airspace granulation tissue. Our results suggest t hat cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue rep air after injury.