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Signal inhibitory receptor on leukocytes-1 (SIRL-1) negatively regulates the oxidative burst in human phagocytes.
Steevels, Tessa A M; van Avondt, Kristof; Westerlaken, Geertje H A; Stalpers, Femke; Walk, Jona; Bont, Louis; Coffer, Paul J; Meyaard, Linde.
Afiliação
  • Steevels TA; Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Eur J Immunol ; 43(5): 1297-308, 2013 May.
Article em En | MEDLINE | ID: mdl-23436183
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fagócitos / Monócitos / Receptores Imunológicos / Explosão Respiratória / Espécies Reativas de Oxigênio / Neutrófilos Tipo de estudo: Observational_studies Limite: Humans / Infant Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fagócitos / Monócitos / Receptores Imunológicos / Explosão Respiratória / Espécies Reativas de Oxigênio / Neutrófilos Tipo de estudo: Observational_studies Limite: Humans / Infant Idioma: En Ano de publicação: 2013 Tipo de documento: Article