The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca2+-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades. However, since 1996 there has been controversy and another article showed lack of interactions with saccharides in 1999. Nevertheless, several high affinity saccharide ligands were synthesized in order to utilize their potential in antitumor therapy. Subsequently, protein ligands were introduced as specific binders for Nkrp1 proteins and three dimensional models of receptor/protein ligand interaction were derived from crystallographic data. Finally, for at least some members of the NK cell C-type lectin-like proteins, the "sweet story" was impaired by two reports in recent years. It has been shown that the rat Nkrp1a and CD69 do not bind saccharide ligands such as GlcNAc, GalNAc, chitotetraose and saccharide derivatives (GlcNAc-PAMAM) do not directly and specifically influence cytotoxic activity of NK cells as it was previously described.

• MeSH
• buňky NK * chemie   imunologie   metabolismus   MeSH
• CD antigeny * chemie   imunologie   metabolismus   MeSH
• diferenciační antigeny T-lymfocytů * chemie   imunologie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lektinové receptory NK-buněk - podrodina B * chemie   imunologie   metabolismus   MeSH
• lektiny typu C * chemie   imunologie   metabolismus   MeSH
• lidé MeSH
• oligosacharidy * chemie   imunologie   metabolismus   MeSH
• terciární struktura proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny * MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů * MeSH
• KLRB1 protein, human MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina B * MeSH
• lektiny typu C * MeSH
• oligosacharidy * MeSH

Rheumatoid arthritis is an autoimmunity leading to considerable impairment of quality of life. N-acetyl glucosamine (GlcNAc) has been described previously as a potent modulator of experimental arthritis in animal models and is used for osteoarthritis treatment in humans, praised for its lack of adverse effects. In this study we present a comprehensive immunological analysis of multivalent GlcNAc-terminated glycoconjugate (GC) application in the treatment of collagen-induced arthritis (CIA) and its clinical outcome. We used immunohistochemistry and FACS to describe conditions on the inflammation site. Systemic and clinical effects were evaluated by FACS, cytotoxicity assay, ELISA, cytometric bead array (CBA), RT-PCR and clinical scoring. We found reduced inflammatory infiltration, NKG2D expression on NK and suppression of T, B and antigen-presenting cells (APC) in the synovia. On the systemic level, GCs prevented the activation of monocyte- and B cell-derived APCs, the rise of TNF-α and IFN-γ levels, and subsequent type II collagen (CII)-specific IgG2a formation. Moreover, we detected an increase of anti-inflammatory IL-4 mRNA in the spleen. Similar to the synovia, the GCs caused a significant reduction of NKG2D-expressing NK cells in the spleen without influencing their lytic function. GCs effectively postponed the onset of arthritic symptoms, reduced their severity and in 18% (GN8P) and 31% (GN4C) of the cases completely prevented their appearance. Our data prove that GlcNAc glycoconjugates prevent the inflammatory response, involving proinflammatory cytokine rise, APC activation and NKG2D expression, leading to the attenuation of clinical symptoms. These results support the glycobiological approach to the treatment of collagen-induced arthritis/rheumatoid arthritis (CIA/RA) as a way of bringing new prospects for more effective therapeutic interventions.

• Klíčová slova
• CIA, GlcNAc glycoconjugates, clinical scoring, cytokines, humoral response,
• MeSH
• acetylglukosamin aplikace a dávkování   MeSH
• antigen prezentující buňky účinky léků   imunologie   MeSH
• artritida experimentální farmakoterapie   imunologie   MeSH
• B-lymfocyty účinky léků   imunologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• buňky NK účinky léků   imunologie   MeSH
• cytokiny metabolismus   MeSH
• kultivované buňky MeSH
• lektinové receptory NK-buněk - podrodina K metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední DBA MeSH
• myši MeSH
• revmatoidní artritida farmakoterapie   imunologie   MeSH
• synoviální membrána účinky léků   imunologie   MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylglukosamin MeSH
• cytokiny MeSH
• Klrk1 protein, mouse MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina K MeSH