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Immler, R.* ; Nussbaumer, K.* ; Doerner, A.* ; El Bounkari, O.* ; Huber, S.* ; Abisch, J.* ; Napoli, M.* ; Schmidt, S.* ; Margraf, A.* ; Pruenster, M.* ; Rohwedder, I.* ; Lange-Sperandio, B.* ; Mall, M.A.* ; de Jong, R.J. ; Ohnmacht, C. ; Bernhagen, J.* ; Voehringer, D.* ; Marth, J.D.* ; Frommhold, D.* ; Sperandio, M.*

CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.

Proc. Natl. Acad. Sci. U.S.A. 121:e2319057121 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4-/- mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4-/- mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4-/- compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4-/- eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4-/- eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4-/- eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4-deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Asthma ; Chemokines ; Eosinophil ; Inflammation ; Sialylation; P-selectin; Siglec-f; Leukocyte Recruitment; Endothelial-cells; Inflammation; Eotaxin; Trafficking; Roles; Vivo; Accumulation
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 121, Issue: 19, Pages: , Article Number: e2319057121 Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
Grants NIH HHS
Wellcome Trust