A new look at the pathogenesis of the meconium aspiration syndrome: a role for fetal pancreatic proteolytic enzymes in epithelial cell detachment.

Abstract:

:We hypothesized that fetal pancreatic digestive enzymes play a role in the lung damage after meconium aspiration. We studied the effect of meconium on the A549 alveolar epithelial cell line. The exposure of the cells to 0.5 to 5% meconium resulted in significant disruption of connections between A549 cells and caused dose-dependent cell detachment, without signs of cell death. A protease inhibitor cocktail prevented the A549 cell detachment induced by meconium. After the exposure to 2.5% meconium, a protective effect was quantified by measuring light absorbance by gentian violet stain of still attached cells. The protease inhibitor cocktail and chymostatin showed significant protective effects, increasing the number of attached cells by 135 and 123%, respectively (p < 0.05). Other individual protease inhibitors tested in the detachment assay (AEBSF, leupeptin, E-64, aprotinin, benzamidine, phosphamidon, and aminohexanoic acid) did not offer statistically significant protection. These results afford a new perspective on the pathophysiology of meconium aspiration syndrome (MAS). We speculate that disruption of intercellular connections and cell detachment from the basement membrane are key events in the pathology associated with MAS. The observed protective effects of protease inhibitors suggest that they may be useful in the treatment and/or prophylaxis of MAS.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Ivanov VA,Gewolb IH,Uhal BD

doi

10.1203/PDR.0b013e3181ebd4c3

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

221-4

issue

3

eissn

0031-3998

issn

1530-0447

journal_volume

68

pub_type

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