UNIGE document Professional Article
previous document  unige:44627  next document
add to browser collection
Title

Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling

Authors
Published in European Journal of Immunology. 2005, vol. 35, no. 1, p. 243-51
Abstract Human CD33 is a myeloid-restricted transmembrane protein of the sialic acid-binding Ig-like lectin (Siglec) family. While structural analysis predicts an inhibitory function, it remains unknown under which circumstances CD33 may operate as an inhibitory molecule. Here we show that treatment of human monocytes with anti-CD33 mAb induces the production of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-8. However, decreased CD33 surface expression obtained by RNA interference using cognate small interfering RNA (siRNA) was specifically paralleled by spontaneous cytokine production. Similarly, sialic acid (CD33 ligand) removal from the monocyte surface by neuraminidase resulted in IL-1 beta up-regulation, while the addition of red blood cells or sialyllactosamine (but not lactosamine) reversed the effect of neuraminidase treatment, thus demonstrating the importance of ligand recognition by CD33 for repression of monocyte activation. Finally, inhibition of phosphoinositide 3-kinase (PI3K) dramatically enhanced the IL-1 beta response to anti-CD33 and neuraminidase, while inhibition of p38 mitogen-activated protein kinase (MAPK) abolished it. Simultaneous addition of both inhibitors resulted in low levels of IL-1 beta, suggesting that CD33 exerts an inhibitory role mediated by PI3K, while p38 MAPK signaling is required for IL-1 beta production. These data indicate that by controlling monocyte activation, CD33 is a key molecule in the inflammatory response, depending on the sialic acid microenvironment for its repressor activity.
Keywords Antibodies, Monoclonal/administration & dosageAntigens, CD/genetics/metabolismAntigens, Differentiation, Myelomonocytic/genetics/metabolismGene SilencingHumansImmunity, InnateInflammation/etiology/immunology/metabolismInterleukin-1/biosynthesisInterleukin-8/biosynthesisMonocytes/immunology/metabolismN-Acetylneuraminic Acid/metabolismPhosphatidylinositol 3-Kinases/metabolismSialic Acid Binding Ig-like Lectin 3Signal TransductionTumor Necrosis Factor-alpha/biosynthesisP38 Mitogen-Activated Protein Kinases/metabolism
Identifiers
PMID: 15597323
Full text
Article (Published version) (273 Kb) - public document Free access
Structures
Research group La matrice extracellulaire (651)
Citation
(ISO format)
LAJAUNIAS, Frédéric, DAYER, Jean-Michel, CHIZZOLINI, Carlo. Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling. In: European Journal of Immunology, 2005, vol. 35, n° 1, p. 243-51. https://archive-ouverte.unige.ch/unige:44627

164 hits

59 downloads

Update

Deposited on : 2015-01-07

Export document
Format :
Citation style :