Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Basophils / immunology
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Basophils / metabolism
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Blotting, Northern
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Bronchoalveolar Lavage Fluid / cytology
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Budesonide
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Calcium / metabolism
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Cell Movement
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Cells, Cultured / metabolism
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Chemokine CCL11
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Chemokine CCL4
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Chemokine CCL5 / genetics
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Chemokine CCL5 / pharmacology
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Chemokine CCL5 / physiology
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Chemokine CCL7
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Chemokines, CC*
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Chemotaxis
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Cytokines / genetics
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Cytokines / pharmacology
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Cytokines / physiology
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DNA, Complementary / analysis
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Eosinophils / immunology
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Eosinophils / metabolism*
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Eosinophils / physiology*
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Epithelial Cells
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Histamine Release
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Humans
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Interleukin-3 / pharmacology
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Macrophage Inflammatory Proteins / pharmacology
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Mice
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Molecular Sequence Data
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Monocyte Chemoattractant Proteins / genetics
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Monocyte Chemoattractant Proteins / metabolism*
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Monocyte Chemoattractant Proteins / pharmacology
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Monocyte Chemoattractant Proteins / physiology*
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Neutrophils / immunology
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Neutrophils / metabolism
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Polymerase Chain Reaction
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Pregnenediones / pharmacology
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Protein Binding / drug effects
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RNA, Messenger / metabolism
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / physiology
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Sequence Homology, Amino Acid
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Transfection
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Tumor Cells, Cultured / metabolism
Substances
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CCL11 protein, human
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CCL13 protein, human
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CCL7 protein, human
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Ccl11 protein, mouse
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Ccl7 protein, mouse
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Chemokine CCL11
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CCL7
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Chemokines, CC
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Cytokines
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DNA, Complementary
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Interleukin-3
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Macrophage Inflammatory Proteins
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Monocyte Chemoattractant Proteins
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Pregnenediones
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RNA, Messenger
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Receptors, Cell Surface
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Budesonide
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Calcium