Abstract
The β2 integrin LFA–1 (lymphocyte function associated antigen; CD11a/CD18) is the common ligand for the intercellular adhesion molecules1,2,3,4 (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 lymphocytes3,4. Integrins can also serve to activate functions associated with distinct subunits of other integrins5. In addition to LFA–1, neutrophils express the β2 integrin Mac–1 (CD11b/CD18; CR3) that apparently contains multiple sites that bind invading microbes directly or through surface–fixed C3 (ref. 6), resulting in activation of the phagocyte function7,8,9,10,11. Expression of the LFA–1 counter–receptor ICAM–1 on endothelial cells occurs only at the site of inflammation12,13. 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.
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Acknowledgements
We thank R. Holland for technical assistance. We are grateful to O. Kühnemund for testing for anti–M antibodies and to C.R. Jr. Cooper for critical reading of the manuscript.
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Schnitzler, N., Haase, G., Podbielski, A. et al. A co-stimulatory signal through ICAM-β2 integrin-binding potentiates neutrophil phagocytosis. Nat Med 5, 231–235 (1999). https://doi.org/10.1038/5597
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DOI: https://doi.org/10.1038/5597
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