Meconium Stimulates Neutrophil Oxidative Burst

Abstract

Acute lung injury induced by meconium aspiration is characterized by rapidly developing pulmonary inflammation with influx of activated polymorphonuclear cells. To evaluate the role of meconium in the activation of these invading cells, we described the oxidative capacity of circulating neutrophils after intratracheal administration of thick human meconium in pigs. We also examined the direct effects of varying meconium concentrations on the oxidative burst of human neutrophils in vitro. In neutrophils isolated from meconium-insufflated pigs, phorbol myristate acetate stimulation led to an average 11.7-fold increase in production of reactive oxygen species, measured by chemiluminescence, whereas the increase in control cells from saline-instilled pigs was only 3.1-fold, p =.012 between the groups. Activation of unstimulated human leukocytes by meconium resulted in a dose-dependent response. The lowest meconium concentration (0.2 mg/mL) had an inhibitory effect on neutrophil activation, whereas higher concentrations of meconium (1 and 2 mg/mL) increased neutrophil oxygen radical production progressively. These results thus indicate that moderate and high concentrations of aspirated meconium rapidly activate circulating neutrophils with a resulting oxidative burst contributing to pulmonary tissue injury, whereas low contamination of the aspirated material may in fact suppress the development of oxidative lung injury.

Constrictor Action of Substances in the Pulmonary Artery in Newborn with the Amnional Fluid Aspiration Syndrome (MAS)

“…Superoxide also increases the relaxation of musculature by entering into reaction with oxygen and by reducing bioavailability of the nitric oxide. Role of the oxygen in changing of the reaction of the smooth musculature of pulmonary artery is related with the syndrome of aspiration of the meconial fluid; this is also reported by other authors [27][28][29][30][31].…”

Studies of meconium-induced lung injury: inflammatory cytokine expression and apoptosis

“…4,8,10,18 Ex vivo studies using a piglet model show that moderate and high concentrations of aspirated meconium rapidly activate circulating neutrophils. 19 Experimental study in piglet model suggests that meconium-induced inflammation is localized in the meconium-contaminated areas of the lungs with no generalized inflammatory injury. 20 Correspondingly, local accumulation of neutrophils and macrophages and production of IL-1b and tumor-necrosis factor-a (TNFa) cytokines have been observed.…”

“…29 Neutrophil influx following meconium exposure may also activate alveolar macrophages to produce oxygen radicals, which may, at least in part, explain the proapoptotic effect of meconium in animal and human lungs. 17,19 Nitric oxide and apoptosis Although the bulk of evidence indicates that nitric oxide (NO) may induce apoptosis in different cell lines, including macrophages, it may have a dual effect. It is interesting to note that inhaled smaller quantities of NO may also inhibit apoptosis.…”

The role of complement in meconium aspiration syndrome

“…30 Recently, it has been showed that meconium has an inhibitory effect on neutrophils in low concentrations (0.2 mg ml À1 ) but in higher concentrations (1 and 2 mg ml À1 ) stimulates neutrophil oxygen radical production progressively. 31 A possible role for complement in meconium-induced oxidative burst has been recently postulated (see below).…”