Published online February 25, 2008
PEDIATRICS Vol. 121 No. 3 March 2008, pp. e496-e505 (doi:10.1542/peds.2007-0878)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Salvesen, B.
Right arrow Articles by Mollnes, T. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Salvesen, B.
Right arrow Articles by Mollnes, T. E.
Related Collections
Right arrow Nutrition & Metabolism

ARTICLE

Role of Complement and CD14 in Meconium-Induced Cytokine Formation

Bodil Salvesen, MDa,b, Michael Fung, PhDc, Ola D. Saugstad, MD, PhDb and Tom E. Mollnes, MD, PhDa

a Institute of Immunology
b Department of Pediatric Research, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
c Tanox Inc, Houston, Texas

OBJECTIVE. Meconium aspiration syndrome has a complex, poorly defined pathophysiology. Meconium is a potent activator of complement in vitro and in vivo; the latter is associated with a systemic inflammatory response. The complement system and Toll-like receptors are 2 important upstream components of the innate immune system that act partly independently in the inflammatory network. The aim of this study was to investigate the relative role of complement and CD14 in meconium-induced cytokine production.

METHODS. Human adult (n = 6) and cord whole blood (n = 6) anticoagulated with lepirudin was collected and distributed into tubes that contained inhibitory antibodies (anti-CD14, anti-C2, anti–factor D, or combinations thereof). The tubes were preincubated for 5 minutes before addition of meconium or buffer and then incubated for 4 hours at 37°C. Complement activation was measured by quantification of the terminal sC5b-9 complement complex by enzyme-linked immunosorbent assay. A panel of 27 inflammatory mediators (cytokines, chemokines, and growth factors) was measured by using multiplex technology.

RESULTS. Fourteen of the 27 mediators measured were induced by meconium both in cord and adult blood. In cord blood, 2 additional chemokines were induced and the inflammatory response was, in general, more potent. Blocking of complement or CD14 differentially reduced the formation of most mediators, anti-CD14 being more effective. Notably, the combined inhibition of complement and CD14 almost completely abolished meconium-induced formation of the cytokines and the chemokines and markedly reduced the formation of growth factors. The endogenous lipopolysaccharide content of meconium could not explain the CD14-mediated response.

CONCLUSIONS. Meconium-induced triggering of the cytokine network is differentially mediated by complement and CD14. A combined inhibition of these effector mechanisms may be an alternative approach to reduce the inflammatory reaction in meconium aspiration syndrome.

Key Words: meconium • complement system • lipopolysaccharide • CD14 • Toll-like receptor • cord blood

Abbreviations: MAS—meconium aspiration syndrome • TNF-{alpha}—tumor necrosis factor {alpha} • IL—interleukin • TLR—Toll-like receptor • PBS—phosphate-buffered saline • IgG1—immunoglobulin G1 • TCC—terminal sC5b-9 complement complex • ELISA—enzyme-linked immunosorbent assay • AU—arbitrary units • IFN-{gamma}—interferon {gamma} • MIP—macrophage inflammatory protein • G-CSF—granulocyte colony-stimulating factor • GM-CSF—granulocyte macrophage colony-stimulating factor • FGF—fibroblast growth factor • VEGF—vascular endothelial growth factor • IP-10—interferon-inducible protein

Accepted Jul 19, 2007.