Trends in Immunology
ReviewSulfated L-selectin ligands as a therapeutic target in chronic inflammation
Section snippets
PNAd and the sialyl 6-sulfo Lewis X determinant in lymphocyte homing
Investigations of lymphocyte recirculation resulted in the discovery of L-selectin as the ‘lymph node homing receptor’ involved in the interaction of lymphocytes with high endothelial venules (HEVs) of lymph nodes 1, 2. Further study revealed that L-selectin mediates the rolling interaction of lymphocytes with HEVs, the first step in a cascade of adhesive and signaling steps that culminate in the delivery of lymphocytes (naive T and B cells, and central memory T cells) into lymph nodes 3, 4.
Sulfotransferases involved in PNAd synthesis
Unsurprisingly, the enzymes involved in the critical post-translational modifications of PNAd have attracted a lot of interest from glycobiologists. With respect to fucosylation, sialylation, core-2 branching and the extension of the core-1 branch, considerable progress has been made in identifying the crucial enzymes, or at least prime candidates, for the biological activities 5, 16, 17. The importance of GlcNAc-6-sulfation to both sialyl 6-sulfo Lewis X and the MECA-79 epitope has motivated
PNAd induction during chronic inflammation
It has long been known that PNAd+ vessels are induced at many sites of chronic inflammation in animal models and humans [5]. In human diseases, the most completely documented examples include cutaneous sites of chronic inflammation, bronchial asthma, rheumatoid arthritis (RA), heart allografts, kidney allografts, thyroiditis, and, most recently, gastritis induced by Helicobacter pylori infection 40, 41, 42, 43, 44, 45. In some studies, positive MECA-79 staining has been directly confirmed to
Therapeutic effects of MECA-79
In a limited number of cases, short-term lymphocyte-homing assays have been employed to confirm that MECA-79 staining of vessels at inflammatory sites does, in fact, correspond to functional L-selectin ligands 54, 55. Thus, intravenous MECA-79 injection was found to block the short-term accumulation of adoptively transferred lymphocytes into the inflamed tissues exhibiting PNAd+ vessels. Unfortunately, only limited information has been available about the true pathophysiologic significance of
Acknowledgements
The work reviewed from our laboratory has been supported by NIH grants to S.D.R. (R01 GM57411, R01 GM23547 and P01 HL024136).
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2022, Journal of EthnopharmacologySulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs
2021, VirologyCitation Excerpt :However, MDCK cells did not express Galβ1-4(SO3--6)GlcNAcβ and by extension we infer that they will not have 6-sulfo sialyl LeX and NeuAcα2-3Galβ1-4(SO3--6)GlcNAc. Human GlcNAc6ST-1, which we used in our experiments, can transfer sulfate to the 6-O position of GlcNAc (Uchimura and Rosen, 2006). Therefore, we considered that 6-sulfo sialyl LeX and NeuAcα2-3Galβ1-4(SO3--6)GlcNAc are produced on the cell surface after transfection of GlcNAc6ST-1.
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2021, Molecular and Cellular ProteomicsA sticky wicket: Defining molecular functions for CD34 in hematopoietic cells
2020, Experimental HematologyCitation Excerpt :In HEVs, rare and highly specialized vessels in secondary lymphoid organs (SLOs), CD34-related sialomucins are modified with 6-sulfosialyl Lewis X (sLeX) glycans and they are collectively called peripheral node addressins (PNAds). PNAds (CD34, podocalyxin, GlyCAM-1, MadCAM-1, endomucin, nepmucin, and perhaps others) [76] serve as glycan-dependent adhesive ligands for naïve lymphocytes expressing L-selectin (CD62L). CD62L is a C-type lectin expressed by late MPPs that are lymphoid-primed (LMPPs) and mature leukocytes, but not megakaryocyte/erythroid progenitors (MEPs), in both mice and humans [77,78].
Dioclea violacea lectin ameliorates inflammation in the temporomandibular joint of rats by suppressing intercellular adhesion molecule-1 expression
2019, BiochimieCitation Excerpt :As the TMJ presents a deep tissue arrangement, carrageenan promotes an acute inflammatory condition in which plasma extravasation reaches its peak 1 h upon stimulation [69]. Variability both on level and in structure of glycans on cells can act as indicators of the cell state and functions [59] and the interaction of DVL with GlcNAc and core 1-sLeX could explain the anti-inflammatory effect of DVL due to essential role of these monosaccharides/glycans in the adhesion of leukocytes to endothelial cells [24–27]. The presented findings lead us to suggest that DVL could interacts with core 1-sLeX (via GlcNAc moiety on sLeX structure) of the inflammatory cell surface, decreasing the ICAM-1 expression, blocking its binding to the selectins of endothelial cells and thereby inhibiting the leukocyte rolling to the tissue, decreasing the inflammation.