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: S Stafford, H Li, P A Forsythe, M Ryan, R Bravo, R Alam
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 10 Pg. 4953-60 (May 15 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9144514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ccl7 protein, mouse
• Chemokine CCL2
• Chemokine CCL4
• Chemokine CCL5
• Chemokine CCL7
• Chemokines
• Cytokines
• Macrophage Inflammatory Proteins
• Monocyte Chemoattractant Proteins
• RNA, Messenger
• Interleukin-4
• Ovalbumin

Topics

• Animals
• Asthma (physiopathology)
• Chemokine CCL2 (genetics)
• Chemokine CCL4
• Chemokine CCL5 (genetics)
• Chemokine CCL7
• Chemokines (metabolism)
• Cytokines
• Hypersensitivity (physiopathology)
• Interleukin-4 (genetics)
• Lung (physiology, physiopathology)
• Macrophage Inflammatory Proteins (genetics)
• Mice
• Mice, Inbred BALB C
• Monocyte Chemoattractant Proteins (physiology)
• Ovalbumin (immunology)
• RNA, Messenger (genetics)