Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes.
The pathogenesis of pneumonitis associated with meconium aspiration is poorly understood. To explore the possibility of pulmonary cytotoxicity in association with bile salt exposure and calcium accumulation, we compared cell viability, radiolabeled calcium accumulation, and intracellular [calcium] in the presence and absence of bile salts, chenodeoxycholate, and 3 beta-OH-5-cholenoate. We assessed viability of type II pneumocytes in culture by cell permeability to trypan blue dye, incorporation of leucine into cellular proteins, and cellular morphology. Intracellular calcium concentrations were monitored with fluorescent dye methodology. At micromolar concentrations, the above bile salts increased cell permeability by as much as 9-fold and decreased leucine incorporation by as much as 5-fold. Radiolabeled calcium accumulation increased by as much as 2.5-fold and intracellular [calcium] transiently increased by as much as 6-fold. Studies using bile salts extracted from meconium yielded similar results. Correlation of calcium accumulation to viability studies yielded a direct relationship with cell permeability and an inverse relationship with leucine incorporation. We speculate that bile salt-induced accumulation of intracellular calcium in lung cells may contribute to the pathogenesis of meconium aspiration pneumonitis.
Oelberg
D G
DG
Department of Pediatrics, University of Texas Medical School, Houston 77225.
Downey
S A
SA
Flynn
M M
MM
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008471:Meconium Aspiration Syndrome / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; C026883:3 beta-hydroxychol-3-en-24-oic acid; D002118:Calcium