Association between CD14 polymorphisms and serum soluble CD14 levels: Effect of atopy and endotoxin inhalation

Tricia D LeVan, Olivier Michel, Mieke Dentener, Jörgen Thorn, Francoise Vertongen, Lena Beijer, Fernando D. Martinez

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. Objective: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. Methods: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 μg of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. Results: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. Conclusion: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.

Original languageEnglish (US)
Pages (from-to)434-440.e1
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number2
DOIs
StatePublished - Feb 2008

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Endotoxins
Inhalation
Serum
Protein Binding
C-Reactive Protein
Leukocytes
Transcription Initiation Site
Homozygote
Innate Immunity
Healthy Volunteers
Biomarkers
Alleles
Genotype
lipopolysaccharide-binding protein

Keywords

  • CD14 antigen
  • atopy
  • endotoxin
  • exposure
  • inflammation
  • innate immunity
  • lipopolysaccharide
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Association between CD14 polymorphisms and serum soluble CD14 levels : Effect of atopy and endotoxin inhalation. / LeVan, Tricia D; Michel, Olivier; Dentener, Mieke; Thorn, Jörgen; Vertongen, Francoise; Beijer, Lena; Martinez, Fernando D.

In: Journal of Allergy and Clinical Immunology, Vol. 121, No. 2, 02.2008, p. 434-440.e1.

Research output: Contribution to journalArticle

LeVan, Tricia D ; Michel, Olivier ; Dentener, Mieke ; Thorn, Jörgen ; Vertongen, Francoise ; Beijer, Lena ; Martinez, Fernando D. / Association between CD14 polymorphisms and serum soluble CD14 levels : Effect of atopy and endotoxin inhalation. In: Journal of Allergy and Clinical Immunology. 2008 ; Vol. 121, No. 2. pp. 434-440.e1.
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AB - Background: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. Objective: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. Methods: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 μg of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. Results: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. Conclusion: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.

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