Phospholipase A2 in meconium-induced lung injury

Abstract

Although the triggering mechanisms of tissue inflammation and injury in meconium-contaminated lungs are still unclear, there is increasing evidence to suggest a central role for phospholipase A 2 's (PLA 2 ). In fact, elevated PLA 2 activities together with high enzyme concentrations, especially the amount of pancreatic (group I) secretory PLA 2 (PLA 2 -I), have been detected in human meconium and in meconium-contaminated lungs. Recent data from our laboratory further indicate that human pancreatic PLA 2 , introduced in high amounts within aspirated particulate meconium, is a potent inducer of lung tissue inflammatory injury. Our finding of elevated human PLA 2 -I concentrations in plasma during the first hours after intratracheal meconium administration in newborn piglets further suggests that intrapulmonary aspiration of meconium could also have systemic inflammatory and injurious effects. This, however, remains to be studied in further detail.

Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury

“…PLA 2 present in meconium hydrolyzes saturated lipid components of surfactant dipalmitoylphosphatidylcholine. Released fatty acids and lysophosphatidylcholine damage the alveolar-capillary membrane (Kääpä and Soukka 2008). Other enzymes and cytokines permeate along with the penetrating fluid and further destroy lung epithelial cells.…”

Bacteria and endotoxin in meconium-stained amniotic fluid at term: could intra-amniotic infection cause meconium passage?

“…free fatty acids on the surface of the airway) which may inactivate surfactant [14,214,215]; (3) inflammatory mediators which are contained in meconium, including a broad range of chemokines and cytokines [17,213,216,217], which can recruit inflammatory cells, such as neutrophils, into the lung and mediate a local inflammatory response; (4) complement activation [218–221]; (5) phospholipase A2, which has been detected in human meconium and meconium-contaminated lungs [14,222], and implicated in the induction of lung inflammation; and (6) apoptosis or programmed cell death [17,213,223,224]. Vidyasagar and Zagariya proposed that chemokines and cytokines in MAS can lead to angiotensin II-induced apoptosis of lung cells [19,224,225].…”

An overview of pulmonary surfactant in the neonate: Genetics, metabolism, and the role of surfactant in health and disease

“…Phospholipase-A2, (PLA 2 ) present in meconium, has been found to inhibit the activity of surfactant in vitro in a dose-dependent manner, through the competitive displacement of surfactant from the alveolar film [51]. PLA 2 is also known to induce hydrolysis of DPPC, releasing free fatty acids and lyso-PC which damage the alveolar capillary membrane and induce intrapulmonary sequestration of neutrophils [52]. Exogenous surfactant replacement either as bolus therapy or with a diluted surfactant lung lavage have been shown to reverse the hypoxemia and reduce pneumothoraces caused by meconium aspiration, decrease requirement for extracorporeal membrane oxygenation (ECMO), decrease duration of oxygen therapy and mechanical ventilation, and reduce the duration of hospital stays [47, 53].…”