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

Cristiana Stellato, Paul Collins, Paul D. Ponath, Dulce Soler, Walter Newman, Greg La Rosa, Haodong Li, John White, Lisa M. Schwiebert, Carol Bickel, Mark Liu, Bruce S. Bochner, Timothy Williams, Robert P. Schleimer

Research output: Contribution to journalArticle

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-1α. 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.

Original languageEnglish (US)
Pages (from-to)926-936
Number of pages11
JournalJournal of Clinical Investigation
Volume99
Issue number5
DOIs
StatePublished - Mar 1 1997

Keywords

  • allergy
  • chemokines
  • eosinophils
  • glucocorticoids
  • inflammation

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    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. (1997). Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines. Journal of Clinical Investigation, 99(5), 926-936. https://doi.org/10.1172/JCI119257