Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma
Top Cited Papers
- 1 September 2000
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 1 (3), 221-226
- https://doi.org/10.1038/79759
Abstract
The prevalence and severity of allergic asthma continue to rise, lending urgency to the search for environmental triggers and genetic substrates. Using microarray analysis of pulmonary gene expression and single nucleotide polymorphism-based genotyping, combined with quantitative trait locus analysis, we identified the gene encoding complement factor 5 (C5) as a susceptibility locus for allergen-induced airway hyperresponsiveness in a murine model of asthma. A deletion in the coding sequence of C5 leads to C5-deficiency and susceptibility. Interleukin 12 (IL-12) is able to prevent or reverse experimental allergic asthma. Blockade of the C5a receptor rendered human monocytes unable to produce IL-12, mimicking blunted IL-12 production by macrophages from C5-deficient mice and providing a mechanism for the regulation of susceptibility to asthma by C5. The role of complement in modulating susceptibility to asthma highlights the importance of immunoregulatory events at the interface of innate and adaptive immunity in disease pathogenesis.Keywords
This publication has 29 references indexed in Scilit:
- Identification of a Coordinate Regulator of Interleukins 4, 13, and 5 by Cross-Species Sequence ComparisonsScience, 2000
- Receptor mediated subversion of macrophage cytokine production by intracellular pathogensCurrent Opinion in Immunology, 1999
- IMMUNOLOGIC BASIS OF ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESSAnnual Review of Immunology, 1999
- The complement system and adaptive immunitySeminars in Immunology, 1998
- A genome-wide search for asthma susceptibility loci in ethnically diverse populationsNature Genetics, 1997
- Mechanism of Suppression of Cell-Mediated Immunity by Measles VirusScience, 1996
- Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice.The Journal of Experimental Medicine, 1995
- C5A Anaphylatoxin and Its Seven Transmembrane-Segment ReceptorAnnual Review of Immunology, 1994
- Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide‐stimulated monocytes and macrophagesEuropean Journal of Immunology, 1990
- Macrophage type 3 complement receptors mediate serum-independent binding of Leishmania donovani. Detection of macrophage-derived complement on the parasite surface by immunoelectron microscopy.The Journal of Experimental Medicine, 1986