The role of complement in meconium aspiration syndrome

Meconium aspiration syndrome: challenges and solutions

“…24 • Complement activation: A recent hypothesis suggests that meconium activates the two main recognition systems of innate immunity, toll-like receptors and complement system, leading not only to lung dysfunction but also to a systemic inflammatory response. 23,25 Despite an increasing focus on lung inflammation in MAS, the cellular mechanisms initiating this inflammatory cascade remain to be clarified.…”

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

“…In response to meconium aspiration, synthesis of various cytokines together with release of active inflammatory cells had been observed (30). Although we do not know the particular responsible component, in vitro, meconium was found to activate both the complement (31,32) and Toll-like receptors (TLR; 33,34)-two important components of the innate immune system.…”

“…The exact time course has not yet been described; however, under conditions of LPS-induced lung injury model, neutrophil influx and activation can be seen within 2h (69), and in experimental models of MAS, influx of polymorphonuclear leukocytes, T-lymphocytes, and monocytes is also demonstrated within few hours (22,30,31,70) which are being associated with decrease of leukocyte count in peripheral blood (6). Meanwhile, TLR and complement activation take place (32,33). Meconium-induced TLR4 inflammation is related to different types of cells, including macrophages, EnC, and EpC and works via activation of NF-κB and AP-1, resulting in IFN and cytokine (such as TNF-α) production (34).…”

“…There is broad spectrum of evidence that complement and TLR pathways are interrelated in many cross-points, so that distinct mediators of both systems share the same signalization pathways (54). Activation of complement by meconium (36) may intensify downstream signalization, and consequent chemokines and adhesion molecules worsen the situation in the lungs by additional leukocyte sequestration (32). Along with IL-8, the complement activation product C5a is one of the most potent chemotactic factors released during inflammation with possible role of neutrophil activator as well (35).…”

“…Once activated, C5a product of complement triggers production of innumerable inflammatory mediators such as cytokines, chemokines, arachidonic acid metabolites, reactive oxygen metabolites, adhesion molecules, and others, resulting in interaction between endothelial cells (EnC) and leukocytes (32). In light of three possible ways of complement activation (classical, alternative, and lectin pathway), meconium was found to work in vitro via the alternative pathway (35) as well as the lectin pathway with subsequent increase of TNF-α, IL-1β, IL-6, IFN-γ, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, and eotaxin (36).…”