Regulation of cytokine expression and leukotriene formation in human basophils by growth factors, chemokines and chemotactic agonists

Eur J Immunol. 1999 Jan;29(1):11-22. doi: 10.1002/(SICI)1521-4141(199901)29:01<11::AID-IMMU11>3.0.CO;2-B.

Abstract

Basophils stimulated with IL-3 plus C5a selectively express IL-4 and IL-13 and continuously produce leukotrienes (LT) for hours. C5a combined with IL-5 or granulocyte-macrophage colony-stimulated factor was, however, much less effective in promoting cytokine expression and a late continuous phase of LTC4 production, possibly due to lower expression levels of their receptor alpha chains. Basophils also express several chemoattractant receptors, including high levels of C5a receptors, macrophage chemotactic protein (MCP) receptors (CCR2) and eotaxin receptors (CCR3), intermediate levels of CXCR1, CXCR2 and platelet-activating factor receptors, and lower levels of N-formyl-Met-Leu-Phe (fMLP) receptors. However, among the corresponding agonists, only C5a, fMLP and much more weakly MCP1, were found to induce cytokine expression and continuous LTC4 release, and only when combined with IL-3. CCR3, which is highly expressed on basophils and has been shown to mediate strong migratory but weak release responses, does not regulate cytokine expression. The weakly expressed fMLP receptor is an efficient activator of several cell functions including LTC4 formation, while CXCR2 hardly affects basophil function despite considerable expression. Thus, chemoattractant-receptors mediate different cellular responses unrelated to their expression levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / drug effects*
  • Basophils / immunology*
  • Basophils / metabolism
  • Chemokines / pharmacology*
  • Chemotactic Factors / agonists
  • Chemotactic Factors / pharmacology
  • Complement C5a / pharmacology
  • Cytokines / biosynthesis*
  • Growth Substances / pharmacology*
  • Humans
  • In Vitro Techniques
  • Interleukin-4 / biosynthesis
  • Leukotriene C4 / biosynthesis
  • Leukotrienes / biosynthesis*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Receptors, Chemokine / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-3 / metabolism
  • Receptors, Interleukin-5

Substances

  • Chemokines
  • Chemotactic Factors
  • Cytokines
  • Growth Substances
  • Leukotrienes
  • Receptors, Chemokine
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptors, Interleukin
  • Receptors, Interleukin-3
  • Receptors, Interleukin-5
  • Interleukin-4
  • Leukotriene C4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Complement C5a