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

Susan Stafford, Huamin Li, Patricia A. Forsythe, Matthew Ryan, Rodrigo Bravo, Rafeul Alam

Research output: Contribution to journalArticle

69 Scopus citations

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-1α, 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-1α 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.

Original languageEnglish (US)
Pages (from-to)4953-4960
Number of pages8
JournalJournal of Immunology
Volume158
Issue number10
StatePublished - May 15 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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