Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma.

Karp, C L; Grupe, A; Schadt, E; Ewart, S L; Keane-Moore, M; Cuomo, P J; Köhl, J; Wahl, L; Kuperman, D; Germer, S; Aud, D; Peltz, G; Wills-Karp, M

Karp, C L; Grupe, A; Schadt, E; Ewart, S L; Keane-Moore, M; Cuomo, P J; Köhl, J; Wahl, L; Kuperman, D; Germer, S; Aud, D; Peltz, G; Wills-Karp, M.

Afiliación

Karp CL; Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MA, USA. mkarp@wekh.jhu.edu

Nat Immunol ; 1(3): 221-6, 2000 Sep.

Article en En | MEDLINE | ID: mdl-10973279

RESUMEN

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.

Asunto(s)

Asma/genética; Complemento C5/genética; Animales; Asma/inmunología; Asma/metabolismo; Células Cultivadas; Complemento C5/inmunología; Modelos Animales de Enfermedad; Predisposición Genética a la Enfermedad/genética; Humanos; Interleucina-12/biosíntesis; Macrófagos Peritoneales/inmunología; Macrófagos Peritoneales/metabolismo; Masculino; Ratones; Ratones Endogámicos AKR; Ratones Endogámicos BALB C; Ratones Endogámicos C3H; Ratones Endogámicos C57BL; Monocitos/inmunología; Monocitos/metabolismo; Análisis de Secuencia por Matrices de Oligonucleótidos; Polimorfismo de Nucleótido Simple

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Complemento C5 Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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