Role of mesenchymal cell death in lung remodeling after injury.

Abstract

Repair after acute lung injury requires elimination of granulation tissue from the alveolar airspace. We hypothesized that during lung repair, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, would 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 proliferating cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination of lung tissue from patients after lung injury revealed evidence of apoptotic cells within airspace granulation tissue. Our results suggest that cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue repair after injury. (J. Clin. Invest. 1993. 92:388-397.)

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

“…The adult literature suggests that mesenchymal cells may have a role in acute lung injury and persistent acute respiratory distress syndrome. [20][21][22] However, their role in neonatal lung injury has not been adequately analyzed. As ECMO is often used as a therapy for neonates with acute lung injury, our findings suggest MSCs may be isolated from newborns so to evaluate their role in the repair process of neonatal lung injury.…”

Unscheduled apoptosis during acute inflammatory lung injury

“…Alternatively, a protective role for apoptosis might have been impaired by the failue to effectively remove the dead cells during ALI, leading to inflammation. Regardless of the role of apoptosis during the acute and inflammatory phase, during repair from injury apoptosis appears to have an important and protective role in the removal of injured cells from lung (Polunovsky, 1993;Uhal, 1995). However, the occurrence of apoptosis in the early and inflammatory phase seems to have substantially different biological consequences than during repair.…”

“…The presence of apoptosis in acutely injured lung could be part of a protective mechanism to limit the extent of injury or inflammation, as has been proposed during resolution of acute respiratory distress syndrome (Polunovsky, 1993;Uhal, 1995). If apoptosis is also protective during acute lung injury, animals that are relatively resistant to such injury might be predicted to exhibit apoptosis sooner than sensitive animals.…”

Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1

“…DNA histograms were analysed using Cell Quest software and cells with hypodiploid DNA content were de®ned as apoptotic. For each experimental condition, apoptosis was con®rmed using TUNEL, acridine orange staining, or ultrastructural analysis as previously described (Polunovsky et al, 1993(Polunovsky et al, , 1994(Polunovsky et al, , 1996.…”