A co-stimulatory signal through ICAM-beta2 integrin-binding potentiates neutrophil phagocytosis

Nat Med. 1999 Feb;5(2):231-5. doi: 10.1038/5597.


The beta2 integrin LFA-1 (lymphocyte function associated antigen; CD11a/CD18) is the common ligand for the intercellular adhesion molecules (ICAMs). Integrins support cell function by providing co-stimulatory second signals that are a precondition for full cell activation first described for ICAM-1-binding to LFA-1 in lymphocytes. Integrins can also serve to activate functions associated with distinct subunits of other integrins. In addition to LFA-1, neutrophils express the beta2 integrin Mac-1 (CD11b/CD18; CR3) that apparently contains multiple sites that bind invading microbes directly or through surface-fixed C3, resulting in activation of the phagocyte function. Expression of the LFA-1 counter-receptor ICAM-1 on endothelial cells occurs only at the site of inflammation. Therefore, in neutrophils, ICAM-1 ligand binding could, as with lymphocytes, also play a part as a co-stimulatory signal to induce full phagocytotic function. We show that in neutrophils, the LFA-1 ligand interaction is the stimulatory signal to express full phagocytotic activation. This is best demonstrated by the rapid association of Streptococcus pyogenes with neutrophils, followed by ingestion, strong oxidative-burst induction and enhanced killing of these bacteria, which are well-known for their resistance to human neutrophil defense. These findings may contribute to the development of therapeutic strategies targeting the modulation of ICAM-1-leukocyte interaction.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Cell Separation
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Models, Immunological
  • Neutrophils / immunology*
  • Phagocytosis*
  • Respiratory Burst
  • Streptococcus pyogenes / immunology


  • Antibodies, Monoclonal
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1