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

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.

• 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.
• Ohnmacht, C.
• Bernhagen, J.
• Voehringer, D.
• Marth, J. D.
• Frommhold, D.
• Sperandio, M.