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

• Published in: Journal of allergy and clinical immunology Vol. 121; no. 2; pp. 434 - 440.e1
• Main Authors: LeVan, Tricia D., PhD, Michel, Olivier, MD, Dentener, Mieke, PhD, Thorn, Jörgen, MD, PhD, Vertongen, Francoise, PhD, Beijer, Lena, PhD, Martinez, Fernando D., MD
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01-02-2008; Elsevier Limited
• Subjects: Administration, Inhalation; Adult; Allergy and Immunology; atopy; C-Reactive Protein - metabolism; CD14 antigen; endotoxin; Endotoxins - administration & dosage; Endotoxins - pharmacology; Ethnicity; exposure; Female; Gene expression; Haplotypes; Humans; Hypersensitivity, Immediate - blood; Hypersensitivity, Immediate - genetics; Immunity, Innate - drug effects; inflammation; Inflammation Mediators; innate immunity; Leukocyte Count; Linkage Disequilibrium; lipopolysaccharide; Lipopolysaccharide Receptors - blood; Lipopolysaccharide Receptors - genetics; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Rodents; Sex Characteristics; single nucleotide polymorphism; Studies; CRP; C-reactive protein; LPS-binding protein; sCD14; single nucleotide polymorphism; Linkage disequilibrium; atopy; Skin prick test; CD14 antigen; innate immunity; exposure; SNP; inflammation; SPT; LD; WBC; Soluble CD14; LBP; lipopolysaccharide; White blood cell; endotoxin
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.08.050

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.