Signal inhibitory receptor on leukocytes-1 (SIRL-1) negatively regulates the oxidative burst in human phagocytes

Tessa A.M. Steevels, Kristof van Avondt, Geertje H.A. Westerlaken, Femke Stalpers, Jona Walk, Louis Bont, Paul J. Coffer, Linde Meyaard

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

41 Citaten (Scopus)

Samenvatting

ROS production is an important effector mechanism mediating intracellular killing of microbes by phagocytes. Inappropriate or untimely ROS production can lead to tissue damage, thus tight regulation is essential. We recently characterized signal inhibitory receptor on leukocytes-1 (SIRL-1) as an inhibitory receptor expressed by human phagocytes. Here, we demonstrate that ligation of SIRL-1 dampens Fc receptor-induced ROS production in primary human phagocytes. In accordance, SIRL-1 engagement on these cells impairs the microbicidal activity of neutrophils, without affecting phagocytosis. The inhibition of ROS production may result from reduced ERK activation, since co-ligation of Fc receptors and SIRL-1 on phagocytes inhibited phosphorylation of ERK. Importantly, we demonstrate that microbial and inflammatory stimuli cause rapid downregulation of SIRL-1 expression on the surface of primary neutrophils and monocytes. In accordance, SIRL-1 expression levels on neutrophils in bronchoalveolar lavage fluid from patients with neutrophilic airway inflammation are greatly reduced. We propose that SIRL-1 on phagocytes sets an activation threshold to prevent inappropriate production of oxygen radicals. Upon infection, SIRL-1 expression is downregulated, allowing microbial killing and clearance of the pathogen.

Originele taal-2Engels
Pagina's (van-tot)1297-1308
Aantal pagina's12
TijdschriftEuropean Journal of Immunology
Volume43
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - apr. 2013
Extern gepubliceerdJa

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