Fas ligand expression coincides with alveolar cell apoptosis in late-gestation fetal lung development.
Apoptosis plays a central role in the cellular remodeling of the developing lung. We determined the spatiotemporal patterns of the cell death regulators Fas and Fas ligand (FasL) during rabbit lung development and correlated their expression with pulmonary and type II cell apoptosis. Fetal rabbit lungs (25-31 days gestation) were assayed for apoptotic activity by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and DNA size analysis. Fas and FasL expression were analyzed by RT-PCR, immunoblot, and immunohistochemistry. Type II cell apoptosis increased significantly on gestational day 28; the type II cell apoptotic index increased from 0.54 +/- 0.34% on gestational day 27 to 3.34 +/- 1.24% on day 28, P < 0.01 (ANOVA). This corresponded with the transition from the canalicular to the terminal sac stage of development. The day 28 rise in epithelial apoptosis was synchronous with a robust if transient 20-fold increase in FasL mRNA and a threefold increase in FasL protein levels. In contrast, Fas mRNA levels remained constant, suggestive of constitutive expression. Fas and FasL proteins were immunolocalized to alveolar type II cells and bronchiolar Clara cells. The correlation of this highly specific pattern of FasL expression with alveolar epithelial apoptosis and remodeling implicates the Fas/FasL system as a potentially important regulatory pathway in the control of postcanalicular alveolar cytodifferentiation.
De Paepe
M E
ME
Department of Pathology, Rhode Island Hospital, Providence, Rhode Island 02903, USA. Monique_DePaepe@brown.edu
Rubin
L P
LP
Jude
C
C
Lesieur-Brooks
A M
AM
Mills
D R
DR
Luks
F I
FI
D000818:Animals; D017209:Apoptosis; D005314:Embryonic and Fetal Development / Q000502:physiology*; D053222:Fas Ligand Protein; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D008168:Lung / Q000166:cytology / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology*; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology / Q000196:embryology; D019014:fas Receptor / Q000235:genetics
D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor