Meconium increases surfactant secretion in isolated rat alveolar type II cells.
One of the underlying causes of pathophysiology of meconium aspiration syndrome is access of meconium to the alveolar space and inhibition of activity of lung surfactant. This study examines the effects of meconium on type II cell function by following surfactant secretion. Isolated rat alveolar type II cells were labeled with [methyl-3H]choline during the initial 21-22 h of incubation. During the subsequent 150 min of incubation, phosphatidylcholine (PC) secretion in the presence of 1% meconium was increased 250 +/- 11% (mean +/- SE, n = 23) over controls. The secretagogue effect was concentration-dependent and reached a maximum at 0.5% meconium. The meconium effect was not due to cellular toxicity as evaluated by vital dye exclusion, lactate dehydrogenase release, and PC synthesis. The secretagogue effect of meconium was associated with the particulate fraction pelleted by centrifugation of the suspension for 1 h at 100,000 x g. Heat treatment of meconium decreased the effect, suggesting the active component to be a protein. The effect of meconium was additive with that of 0.1 mM terbutaline, or 1 mM ATP, suggesting different pathways of action of each agent. The effect of meconium was reduced in the presence of 0.1 mM 4,4'-diisothiocyanato-2,2'-disulfonic acid, or 100 ng/mL surfactant protein A. These agents were previously shown to inhibit surfactant secretion in a stimulus-independent manner. Our results suggest that meconium at low concentrations is not toxic to type II cells, and a component of meconium, possibly a protein, increases PC secretion.
Higgins
S T
ST
Department of Pediatrics, Thomas Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Wu
A M
AM
Sen
N
N
Spitzer
A R
AR
Chander
A
A
D000818:Animals; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008470:Meconium / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants