Article Text

MECONIUM ASPIRATION SYNDROME AND MECHANISMS OF COMPLEMENT ACTIVATION
  1. B Salvesen1,2,
  2. M Harboe1,
  3. O D Saugstad2,
  4. T E Mollnes1
  1. 1Institute of Immunology, Medical Faculty, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
  2. 2Department of Pediatric Research, Medical Faculty, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway

Abstract

Background Meconium aspiration syndrome has a complex pathophysiology. Meconium is a potent activator of the complement system both in vitro and in vivo associated with an inflammatory response. Meconium activates complement via the alternative pathway. Recent studies suggest the involvement of different complement pathways.

Objective The aim of the study was to investigate whether meconium activates complement via several pathways.

Methods Cord whole blood from six healthy donors, anticoagulated with lepirudin was preincubated with C1-inhibitor in different concentrations before adding meconium and incubating for 30 minutes. Early complement activation products were measured. Mannose-binding lectin (MBL) sufficient serum was collected from five healthy donors and used in a final dilution of 1 : 2. Serum was preincubated with anti-MBL before adding meconium and incubated for 30 minutes. The terminal sC5b-9 complex (TCC) and C4d was measured.

Results Meconium-induced complement activation (TCC) was dose-dependently reduced by C1-inhibitor. Meconium-induced formation of the alternative pathway convertase C3bBbP, and C4d (classic and lectin pathway) was dose-dependently reduced by C1-inhibitor. The anti-MBL antibody significantly reduced meconium-induced formation of C4d more than 63% and TCC with 27% in MBL sufficient serum.

Discussion The fact that anti-MBL reduced meconium-induced complement activation and C4d formation in lectin pathway sufficient serum suggests that meconium primarily activates both the alternative pathway and lectin pathway, and that part of the alternative pathway activation may be an amplification of lectin pathway activation.

Conclusion Meconium activates complement via the lectin pathway and alternative pathway. Part of the alternative pathway activation is probably an amplification of lectin pathway activation.

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