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 o f activity of lung surfactant. This study examines the effects of meco nium on type II cell function by following surfactant secretion. Isola ted rat alveolar type II cells were labeled with [methyl-H-3]choline d uring 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 contr ols. 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 r elease, and PC synthesis. The secretagogue effect of meconium was asso ciated with the particulate fraction pelleted by centrifugation of the suspension for 1 h at 100,000 x g. Heat treatment of meconium decreas ed the effect, suggesting the active component to be a protein. The ef fect of meconium was additive with that of 0.1 mM terbutaline, or 1 mM ATP, suggesting different pathways of action of each agent. The effec t of meconium was reduced in the presence of 0.1 mM 4,4'-diisothiocyan ato-2,2'-disulfonic acid, or 100 ng/mL surfactant protein A. These age nts were previously shown to inhibit surfactant secretion in a stimulu s-independent manner. Our results suggest that meconium at low concent rations is not toxic to type II cells, and a component of meconium, po ssibly a protein, increases PC secretion.