Download PDF
Am J Perinatol 2002; 19(5): 279-284
DOI: 10.1055/s-2002-33089
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Meconium Stimulates Neutrophil Oxidative Burst

Hanna R. Soukka1,2 , Markku Ahotupa3 , Merja Ruutu3 , Pekka O. Kääpä1,2
  • 1Research Centre of Applied and Preventive Cardiovascular Medicine
  • 2Department of Pediatrics
  • 3MCA Research Laboratory, Department of Physiology, University of Turku, Turku, Finland
Further Information

Publication History

Publication Date:
09 August 2002 (online)

Also available at
    Permissions and Reprints

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.

KEYWORDS

Lung - meconium - neutrophil - oxidative burst

REFERENCES

  • 1 Cleary C M, Wiswell T E. Meconium-stained amniotic fluid and the meconium aspiration syndrome: an update.  Pediatr Clin North Am . 1998;  45 551-529
    PubMedGoogle Scholar
  • 2 Saugstad O D. Oxygen toxicity in the neonatal period.  Acta Paediatr Scand . 1990;  79 881-892
    PubMedGoogle Scholar
  • 3 Frank L. Developmental aspects of experimental pulmonary oxygen toxicity.  Free Radic Biol Med . 1991;  11 463-494
    CrossrefPubMedGoogle Scholar
  • 4 Davey A M, Becker J D, Davis J M. Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model.  Pediatr Pulmonol . 1993;  16 101-108
    CrossrefPubMedGoogle Scholar
  • 5 Fujishima S, Aikawa N. Neutrophil-mediated tissue injury and its modulation.  Intensive Care Med . 1995;  21 277-285
    CrossrefPubMedGoogle Scholar
  • 6 Siminiak T, Flores N A, Sheridan D J. Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury.  Eur Heart J . 1995;  16 160-170
    PubMedGoogle Scholar
  • 7 Zimmerman J J. Bronchoalveolar inflammatory pathophysiology of bronchopulmonary dysplasia.  Clin Perinatol . 1995;  22 429-456
    PubMedGoogle Scholar
  • 8 de Beaufort J A, Pelikan D MV, Elferink J GR, Berger H M. Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.  Lancet . 1998;  352 102-105
    PubMedGoogle Scholar
  • 9 Yamada T, Minakami H, Matsubara S, Yatsuda T, Kohmura Y, Sato I. Meconium-stained amniotic fluid exhibits chemotactic activity for polymorphonuclear leukocytes in vitro.  J Reprod Immunol . 2000;  46 21-30
    PubMedGoogle Scholar
  • 10 Tyler D C, Murphy J, Cheney F W. Mechanical and chemical damage to lung tissue caused by meconium aspiration.  Pediatrics . 1978;  62 454-459
    PubMedGoogle Scholar
  • 11 Clark P, Duff P. Inhibition of neutrophil oxidative burst and phagocytosis by meconium.  Am J Obstet Gynecol . 1995;  173 1301-1305
    CrossrefPubMedGoogle Scholar
  • 12 Kojima T, Hattori K, Fujiwara T, Sasai-Takedatsu M, Kobayashi Y. Meconium-induced lung injury mediated by activation of alveolar macrophages.  Life Sci . 1994;  54 1559-1562
    CrossrefPubMedGoogle Scholar
  • 13 Soukka H, Rautanen M, Halkola L, Kero P, Kääpä P. Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs.  Pediatr Pulmonol . 1997;  23 205-211
    CrossrefPubMedGoogle Scholar
  • 14 Matsubara S, Yamada T, Minakami H, Takizawa T, Sato I. Meconium-stained amniotic fluid activates polymorphonuclear leukocytes: ultrastructural and enzyme-cytochemical evidence.  Eur J Histochem . 1999;  43 205-210
    PubMedGoogle Scholar
  • 15 Yamada T, Matsubara S, Minakami H, Kohmura Y, Hiratsuka M, Sato I. Chemotactic activity for polymorphonuclear leukocytes: meconium versus meconium-stained amniotic fluid.  Am J Reprod Immunol . 2000;  44 275-278
    CrossrefPubMedGoogle Scholar
  • 16 Wiswell T E, Peabody S S, Davis J M, Slayter M V, Bent R C, Merritt T A. Surfactant therapy and high-frequency jet ventilation in the management of a piglet model of meconium aspiration syndrome.  Pediatr Res . 1994;  36 494-500
    PubMedGoogle Scholar
  • 17 Ryan S F, Ghassibi Y, Liau D F. Effects of activated polymorphonuclear leukocytes upon pulmonary surfactant in vitro.  Am J Respir Cell Mol Biol . 1991;  4 33-41
    PubMedGoogle Scholar
  • 18 Gilliard N, Heldt G P, Loredo J. Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties.  J Clin Invest . 1994;  93 2608-2615
    PubMedGoogle Scholar
  • 19 Clark D A, Nieman G F, Thompson J E, Paskanik A M, Rochar J E, Bredenberg C E. Surfactant displacement by meconium free fatty acids: an alternative explanation for atelectasis in meconium aspiration syndrome.  J Pediatr . 1987;  110 765-770
    PubMedGoogle Scholar
  • 20 Moses D, Holm B A, Spitale P, Liu M, Enhorning G. Inhibition of pulmonary surfactant function by meconium.  Am J Obstet Gynecol . 1991;  164 477-481
    PubMedGoogle Scholar
  • 21 Sun B, Curstedt T, Robertson B. Surfactant inhibition in experimental meconium aspiration.  Acta Paediatr . 1993;  82 182-189
    CrossrefPubMedGoogle Scholar
  • 22 Chao W, Spragg R G, Smith R M. Inhibitory effect of porcine surfactant on the respiratory burst oxidase in human neutrophils.  J Clin Invest . 1995;  96 2654-2660
    PubMedGoogle Scholar
  • 23 Gregory G A, Gooding C A, Phibbs R H, Tooley W H. Meconium aspiration in infants: a prospective study.  J Pediatr . 1974;  85 848-852
    PubMedGoogle Scholar
  • 24 McCord J M. Oxygen-derived free radicals in postischemic tissue injury.  N Engl J Med . 1985;  312 159-163
    PubMedGoogle Scholar
  • 25 Higgins S T, Wu A, Sen N, Spitzer A R, Chander A. Meconium increases surfactant secretion in isolated rat alveolar type II cells.  Pediatr Res . 1996;  39 443-447
    PubMedGoogle Scholar
  • 26 Kääpä P, Kytölä J, Soukka H, Ahotupa M. Human meconium has potent antioxidative properties.  Biol Neonate . 1997;  72 71-75
    PubMedGoogle Scholar
  • 27 Perlman E L, Moore G W, Hutchins G M. The pulmonary vasculature in meconium aspiration.  Hum Pathol . 1989;  20 701-706
    CrossrefPubMedGoogle Scholar
  • 28 Steinhorn R H, Millard S L, Morin F C. Persistent pulmonary hypertension of the newborn: role of nitric oxide and endothelin in pathophysiology and treatment.  Clin Perinatol . 1995;  22 405-428
    PubMedGoogle Scholar
  • 29 Fardy C H, Silverman M. Antioxidants in neonatal lung disease.  Arch Dis Child . 1995;  73 F112-F117
    PubMedGoogle Scholar
  • 30 Tate R M, Morris H G, Schroeder W R, Repine J E. Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.  J Clin Invest . 1984;  74 608-613
    PubMedGoogle Scholar
  • 31 Sanderud J, Norstein J, Saugstad O D. Reactive oxygen metabolites produce pulmonary vasoconstriction in young pigs.  Pediatr Res . 1991;  29 543-547
    PubMedGoogle Scholar