title: Monocyte chemotactic protein-3 (MCP-3)/fibroblast-induced cytokine (FIC) in eosinophilic inflammation of the airways and the inhibitory effects of an anti-MCP-3/FIC antibody.
abstract: Monocyte chemotactic protein-3 (MCP-3)/fibroblast-induced cytokine (FIC), a CC chemokine, is chemotactic for cells that typically infiltrate the late-phase allergic reaction. We developed a mouse model of airway inflammation to study the role of MCP-3/FIC. The immunization of mice with OVA resulted in Ag-specific IgE Ab production and the expression of mRNA for IL-4 in the lung tissue. Two weeks after immunization mice were challenged with the allergen by inhalation. Lungs were lavaged, and the tissue was examined at 2 or 24 h. Allergen challenge resulted in the increased recovery of leukocytes in the lavage fluid, but saline challenge did not. There was a significant increase in eosinophils (29 +/- 8% vs 1.2 +/- 0.2%) and lymphocytes (25 +/- 4% vs 5 +/- 2%) in the bronchoaveolar lavage fluid. Histologic examination of the lung demonstrated intense airway inflammation following OVA challenge. The expression of MCP-3/FIC and other CC chemokines (MCP-1, macrophage inflammatory protein-1alpha, and RANTES) was investigated by reverse transcription-PCR followed by densitometric analyses. The allergen challenge up-regulated the expression of mRNA for MCP-1, MCP-3/FIC, and macrophage inflammatory protein-1alpha at 2 and/or 24 h. Immunocytochemical staining for MCP-3/FIC showed that the allergen challenge induced the expression of MCP-3/FIC predominantly in the airway epithelium. Pretreatment of mice with an anti-MCP-3/FIC Ab significantly inhibited the OVA-induced airway inflammation and the bronchoalveolar lavage eosinophilia (8 +/- 2% vs 46 +/- 11% after control Ab, p < 0.03). We conclude that MCP-3/FIC plays a significant role in the allergen-induced eosinophilic inflammation of the airways.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stafford
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: P A
authors.initials: PA
authors.lastname: Forsythe
authors.forename: M
authors.initials: M
authors.lastname: Ryan
authors.forename: R
authors.initials: R
authors.lastname: Bravo
authors.forename: R
authors.initials: R
authors.lastname: Alam
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics; D054410:Chemokine CCL7; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines; D006967:Hypersensitivity / Q000503:physiopathology*; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000502:physiology* / Q000503:physiopathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018945:Monocyte Chemoattractant Proteins / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C515451:Ccl7 protein, mouse; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D018925:Chemokines; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D010047:Ovalbumin