Apoptosis of airway epithelial cells in response to meconium.
Meconium aspiration syndrome (MAS) is common among newborn children but its mechanism is unclear. The syndrome is known to produce a strong inflammatory reaction in the lungs resulting in massive cell death. In this work we studied lung cell death by apoptosis after meconium aspiration in forty two-week-old rabbit pups. Analyzing lung samples by ISEL-DNA end labeling demonstrated the specific spread of apoptotic bodies throughout the lungs. These bodies were shrunken and smaller in size compared to normal cells and many of them were lacking cell membranes. About 70% of all apoptotic bodies were found among the airway epithelium cell eight hours after meconium instillation. In comparison, among lung alveolar cells, only about 20% cells were apoptotic in the same animals. In meconium-treated lungs and A549 cells, a significant increase of angiotensinogen mRNA and Caspase-3 expression were observed. The pretreatment of cells with Caspase-3 inhibitor ZVAD-fmk significantly inhibited meconium-induced lung cell death by apoptosis. These findings demonstrate the apoptotic process in meconium-instilled lungs or A549 cells in culture. Our results show lung airway epithelial and A549 cell apoptosis after meconium instillation. We suggest that studies of lung airway epithelial cell death are essential to understanding the pathophysiology of MAS and may present a key point in future therapeutic applications.
Zagariya
Alexander
A
Neonatology Laboratories, Department of Pediatrics, Michael Reese Hospital, and Division of Neonatology, University of Illinois at Chicago, 804 S. Wood Street, Chicago, IL 60612, USA. zagariya@uic.edu
Bhat
Rama
R
Chari
Gopal
G
Uhal
Bruce
B
Navale
Shankararao
S
Vidyasagar
Dharmapuri
D
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000808:Angiotensinogen / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008471:Meconium Aspiration Syndrome / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000808:Angiotensinogen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases