Meconium-induced inflammation and surfactant inactivation: specifics of molecular mechanisms

Abstract

This review summarizes neonatal meconium aspiration syndrome in light of meconium-induced inflammation and inflammatory surfactant inactivation, related to both endogenous and therapeutic exogenous surfactant. The wide effect of meconium on surfactant properties is divided into three points. Direct effect of meconium on surfactant properties refers mainly to fragmentation of dipalmitoylphosphatidylcholine and other surfactant phospholipids together with cleavage of surfactant proteins. Initiation of inflammatory response due to activation of receptors by yet unspecified compounds involves complement and Toll-like receptor activation. A possible role of lung collectins, surfactant proteins A and D, which can exert both pro-and anti-inflammatory reactions, is discussed. Initiation of inflammatory response by specified compounds in meconium reflects inflammatory functioning of cytokines, bile acids, and phospholipases contained in meconium. Unifying sketch of many interconnections in all these actions aims at providing integrated picture of inflammatory surfactant inactivation.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome

“…Various anti-inflammatory drugs (such as glucocorticoids, phosphodiesterase inhibitors, angiotensin-converting enzyme inhibitors, cyclooxygenase inhibitors, or antioxidants) have been tested as possible MAS therapies. [7][8][9][10][11] The therapeutic value of these anti-inflammatory agents in the management of MAS is controversial.…”

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“…It also decreases the levels of surfactant proteins A and B and directly harms type II pneumocytes, thereby decreasing surfactant production. 15 In recent clinical trials, improved gas exchange following surfactant treatment was demonstrated in both term and preterm neonates with respiratory conditions other than surfactant deficient RDS, such as meconium aspiration syndrome, bacterial pneumonia and bronchopulmonary dysplasia. 16 Surfactant therapy in MAS is analysed by various researchers.…”

Selective Inhibition of NF-κB and Surfactant Therapy in Experimental Meconium-Induced Lung Injury

“…Meconium-induced surfactant dysfunction is multilevel process, starting with direct effect of meconium on surfactant components and ending with harmful inflammatory and oxidative cascades (Kopincova and Calkovska 2016). Despite confirmed deleterious effect on endogenous surfactant, effectivity of exogenous surfactant given as in newborns with MAS is still discussed.…”

“…When we compared only Mec and Surf group using non-parametric Mann-Whitney U test, significance was marked, in accordance with our previous results, where surfactant treatment prevented oxidative damage in lung tissue and systemic circulation (Kopincová et al 2014, Mikolka et al 2016b. And finally, no change in apoptotic markers suggests that small amount of residual meconium is able to initiate inflammatory cascades which in turn activate each other (Kopincova and Calkovska 2016).…”

“…In vivo, polymorphonuclear activation, free radicals production, cytokine synthesis, phospholipase A 2 -mediated tissue damage, cell apoptosis and edema formation accompanied main feature of this disease -surfactant dysfunction (Vydiasagar and Zagaryia 2008, Mikolka et al 2013, Kopincová et al 2014. What is clinically manifested as serious respiratory failure with the need of exogenous surfactant and ventilatory support, is on the molecular level largely result of many interrelated signaling pathways streaming through activation of nuclear factor κB (NF-κB; reviewed in Kopincova and Calkovska 2016). Since all these inflammatory processes are able to impair administered exogenous surfactant and mitigate the treatment efficacy, inhibition of inflammation is one of the targets of current therapeutic interventions.…”