biostudies-literatureNonaka MNIAID NIH HHSNCI NIH HHS8173-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4050563biostudies-literatureUnknown111(22)Identification of carbohydrate sequences that determine affinity to specific chemokines is a critical step for strategies to interfere with chemokine-mediated leukocyte trafficking. Here, we first characterized the development of allergic asthma in Tie2-dependent and inducible Ext1-knockout (Tie2-Ext1(iKO)) mice. We showed that heparan sulfate is essential for leukocyte recruitment in the peribronchial region and bronchoalveolar lavage fluid (BALF), and is crucial for induction of airway hyperresponsiveness. Our glycan microarray showed a unique affinity profile of chemokine CCL20 to substructures of heparin and heparin-like oligo/di/monosaccharides. Among them, we identified a synthetic and not naturally occurring monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA), as a potentialProceedings of the National Academy of Sciences of the United States of AmericaSynthetic di-sulfated iduronic acid attenuates asthmatic response by blocking T-cell recruitment to inflammatory sites.PMC4050563R01 AI072115AI 107779R01 AI107779R37 AI038425P01 CA071932P01 CA71932AI 70535U19 AI070535AI 38425AI 72115R01 AI038425Nakayama JFukuda MBroide DHSeeberger PHGotze SBao XMatsumura FKononov ANonaka MKandasamy JfalseSynthetic di-sulfated iduronic acid attenuates asthmatic response by blocking T-cell recruitment to inflammatory sites.Identification of carbohydrate sequences that determine affinity to specific chemokines is a critical step for strategies to interfere with chemokine-mediated leukocyte trafficking. Here, we first characterized the development of allergic asthma in Tie2-dependent and inducible Ext1-knockout (Tie2-Ext1(iKO)) mice. We showed that heparan sulfate is essential for leukocyte recruitment in the peribronchial region and bronchoalveolar lavage fluid (BALF), and is crucial for induction of airway hyperresponsiveness. Our glycan microarray showed a unique affinity profile of chemokine CCL20 to substructures of heparin and heparin-like oligo/di/monosaccharides. Among them, we identified a synthetic and not naturally occurring monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA), as a potential2014-01-01T00:00:00Z2014 Jun2025-04-26T09:52:42.689Z2019-03-27T01:29:47ZS-EPMC40505632483517610.1073/pnas.1319870111