Meconium exposure dependent cell death and apoptosis in human alveolar epithelial cells.
Alveolar epithelial cells of neonates are directly exposed to aspirated meconium during meconium aspiration syndrome (MAS). This study was designed to investigate the influence of quantity and time of meconium exposure on the cell viability and caspase activity in type II human alveolar epithelial cells. Human alveolar epithelial cells were incubated with human meconium suspension at different concentrations and for different times. Cell viability and DNA fragmentation were investigated together with caspases activity and the amount of Bcl-2 protein present. We found that cell viability was significantly lower in cells exposed to a higher concentration of meconium. This was also true for cells exposed to meconium for longer. Significantly higher DNA fragmentation, an approximately two- to fivefold increase, was observed in cells that had been exposed to higher (5% and 10%) concentration of meconium compared to those treated with lower (0.1% and 1%) concentrations (P < 0.05). The activity of most apoptotic initiators (caspase 2, 8, 9, 10) and effectors (caspase 3, 6) were found to be significantly higher in cells subject to greater meconium exposure compared to cells with no or minor meconium exposure. The level of Bcl-2 was also found to be significantly decreased in meconium-exposed cells (P < 0.05). In conclusion, human meconium would seem to induce direct cell death as well as caspase-dependent apoptosis in alveolar epithelial cells; the amount and period of exposure to meconium are crucial factors in this process. Thus, removing aspirated meconium should alleviate lung cell damage in neonates and improve the outcome with MAS.
Jeng
Mei-Jy
MJ
Institute of Emergency and Critical Care Medicine, Department of Pediatrics, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. mjjeng@vghtpe.gov.tw
Soong
Wen-Jue
WJ
Lee
Yu-Sheng
YS
Tsao
Pei-Chen
PC
Yang
Chia-Feng
CF
Chiu
Shih-Yun
SY
Tang
Ren-Bin
RB
D017209:Apoptosis; D001688:Biological Products / Q000494:pharmacology; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D008470:Meconium; D008471:Meconium Aspiration Syndrome / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D011663:Pulmonary Surfactants / Q000494:pharmacology
D001688:Biological Products; D019253:Proto-Oncogene Proteins c-bcl-2; D011663:Pulmonary Surfactants; D020169:Caspases; C072197:beractant