Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines

• Published in: The Journal of clinical investigation Vol. 99; no. 5; pp. 926 - 936
• Main Authors: Stellato, C, Collins, P, Ponath, P D, Soler, D, Newman, W, La Rosa, G, Li, H, White, J, Schwiebert, L M, Bickel, C, Liu, M, Bochner, B S, Williams, T, Schleimer, R P
• Format: Journal Article
• Language: English
• Published: United States 01-03-1997
• Subjects: Amino Acid Sequence; Animals; Basophils - immunology; Basophils - metabolism; Blotting, Northern; Bronchoalveolar Lavage Fluid - cytology; Budesonide; Calcium - metabolism; Cell Movement; Cells, Cultured - metabolism; Chemokine CCL11; Chemokine CCL4; Chemokine CCL5 - genetics; Chemokine CCL5 - pharmacology; Chemokine CCL5 - physiology; Chemokine CCL7; Chemokines, CC; Chemotaxis; Cytokines - genetics; Cytokines - pharmacology; Cytokines - physiology; DNA, Complementary - analysis; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - physiology; Epithelial Cells; Histamine Release; Humans; Interleukin-3 - pharmacology; Macrophage Inflammatory Proteins - pharmacology; Mice; Molecular Sequence Data; Monocyte Chemoattractant Proteins - genetics; Monocyte Chemoattractant Proteins - metabolism; Monocyte Chemoattractant Proteins - pharmacology; Monocyte Chemoattractant Proteins - physiology; Neutrophils - immunology; Neutrophils - metabolism; Polymerase Chain Reaction; Pregnenediones - pharmacology; Protein Binding - drug effects; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - physiology; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Transfection; Tumor Cells, Cultured - metabolism
• ISSN: 0021-9738
• DOI: 10.1172/jci119257

Monocyte chemotactic protein-4 (MCP-4) is a newly identified C-C chemokine with potent eosinophil chemoattractant properties. We describe studies of its biological activity in vitro to induce chemotaxis of peripheral blood eosinophils and to induce histamine release from IL-3-primed peripheral blood basophils. MCP-4 and eotaxin caused a similar rise in eosinophil intracytoplasmic Ca2+ and complete cross-desensitization. MCP-4 also abolished the eosinophil Ca2+ response to MCP-3 and partially desensitized the response to macrophage inflammatory protein-1alpha. MCP-4 activated cell migration via either CCR2b or CCR3 in mouse lymphoma cells transfected with these chemokine receptors. MCP-4 inhibited binding of 125I-eotaxin to eosinophils and CCR3-transfected cells and inhibited 125I-MCP-1 binding to CCR2b-transfectants. MCP-4 mRNA was found in cells collected in bronchoalveolar lavage of asthmatic and nonasthmatic subjects and was prominently expressed in human lung and heart. MCP-4 mRNA was expressed in several human bronchial epithelial cell lines after cytokine stimulation. Pretreatment of BEAS-2B epithelial cells with the glucocorticoid budesonide inhibited MCP-4 mRNA expression. These features make MCP-4 a candidate for playing a role in eosinophil recruitment during allergic respiratory diseases.