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

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Article Abstract

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of mice. Ex vivo flow chamber assays uncovered reduced adhesion of compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated 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 -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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087806PMC
http://dx.doi.org/10.1073/pnas.2319057121DOI Listing

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