title: Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3.
abstract: Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients are skin-prick test negative to common aeroallergens and have total serum immunoglobulin E concentrations within the normal range. However both atopic and nonatopic asthma are characterized by chronic inflammation of the bronchial mucosa in which eosinophils are prominent and are believed to be associated with local tissue damage. Therefore, specific eosinophil chemoattractants acting in concert with factors which prolong eosinophil survival may at least partly account for selective eosinophil recruitment to the asthmatic bronchial mucosa. The CC chemokines RANTES and monocyte chemotactic protein 3 (MCP-3) are potent eosinophil chemotactic factors, while the cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor (GM-CSF), and IL-3 prolong eosinophil survival. We have tested the hypothesis that elevated numbers of cells expressing mRNA for RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 are present in bronchial biopsies from atopic and nonatopic asthmatics compared with atopic and nonatopic nonasthmatic controls. The technique of in situ hybridization using 35S-labeled riboprobes was employed to detect mRNA+ bronchial mucosal cells. Compared with controls we observed significant increases in the numbers of cells expressing RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 (all P values < 0.001) in atopic and nonatopic asthmatics. These observations support the view that atopic and nonatopic asthma are associated with combined bronchial mucosal expression of CC chemokines (RANTES and MCP-3), together with eosinophil-active cytokines (IL-5, GM-CSF, and IL-3). These cytokines might contribute to the bronchial mucosal accumulation of activated eosinophils in both atopic and nonatopic variants of asthma.
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: S
authors.initials: S
authors.lastname: Ying
authors.forename: C
authors.initials: C
authors.lastname: Corrigan
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: J
authors.initials: J
authors.lastname: Barkans
authors.forename: R
authors.initials: R
authors.lastname: Pfister
authors.forename: Q
authors.initials: Q
authors.lastname: Meng
authors.forename: J
authors.initials: J
authors.lastname: Van Damme
authors.forename: G
authors.initials: G
authors.lastname: Opdenakker
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
mesh_terms: D001249:Asthma / Q000235:genetics*; D001980:Bronchi / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000235:genetics*; D054410:Chemokine CCL7; D016207:Cytokines / Q000235:genetics*; D004804:Eosinophils / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D017403:In Situ Hybridization; D007377:Interleukin-3 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics*; D009092:Mucous Membrane / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C515450:CCL7 protein, human; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor