Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production

Blood. 2005 Oct 1;106(7):2543-50. doi: 10.1182/blood-2005-03-1239. Epub 2005 Jun 14.

Abstract

Dectin-1 is a lectin receptor for beta-glucan that is important for innate macrophage recognition of fungi and contributes to phagocytosis, reactive oxygen production, and induction of inflammatory cytokines. The mechanisms by which Dectin-1 mediates intracellular signaling are just beginning to be defined. Spleen tyrosine kinase (Syk) is a protein tyrosine kinase that is critical for adaptive immune responses where it mediates signaling through B-cell receptors, T-cell receptors, and Fc receptors. Here we report that Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production, but not for phagocytosis. Syk activation is restricted to a subpopulation of macrophages that is in equilibrium with cells that cannot activate the pathway. The proportion of macrophages using this signaling pathway can be modulated by cytokine treatment. Thus, Dectin-1 signaling reveals dynamic macrophage heterogeneity in inflammatory activation potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / metabolism
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Erythrocytes / metabolism
  • Flow Cytometry
  • Humans
  • Inflammation
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Macrophages / metabolism*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Microscopy, Fluorescence
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Phagocytosis
  • Protein-Tyrosine Kinases / metabolism*
  • Reactive Oxygen Species*
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Fc / metabolism
  • Sheep
  • Signal Transduction
  • Streptavidin / pharmacology
  • Syk Kinase
  • Transfection

Substances

  • Cytokines
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Reactive Oxygen Species
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Receptors, Fc
  • dectin 1
  • Streptavidin
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse