Interleukin-3 promotes the expression of E-NPP3/CD203C on human blood basophils in healthy subjects and in patients with birch pollen allergy

• Published in: International journal of immunopathology and pharmacology Vol. 20; no. 2; p. 267
• Main Authors: Hauswirth, A W, Sonneck, K, Florian, S, Krauth, M T, Bohm, A, Sperr, W R, Valenta, R, Schernthaner, G H, Printz, D, Fritsch, G, Buhring, H J, Valent, P
• Format: Journal Article
• Language: English
• Published: England 01-04-2007
• Subjects: Antigens, CD - biosynthesis; Antigens, CD - genetics; Basophils - immunology; Basophils - metabolism; Betula - immunology; Cells, Cultured; Gene Expression Regulation - physiology; Humans; Interleukin-3 - physiology; Phosphoric Diester Hydrolases - biosynthesis; Phosphoric Diester Hydrolases - genetics; Platelet Membrane Glycoproteins - biosynthesis; Platelet Membrane Glycoproteins - genetics; Pollen - immunology; Pyrophosphatases - biosynthesis; Pyrophosphatases - genetics; Rhinitis, Allergic, Seasonal - immunology; Tetraspanin 30
• ISSN: 0394-6320
• DOI: 10.1177/039463200702000207

We recently identified the ectoenzyme CD203c as a novel basophil activation antigen that is upregulated in response to FcepsilonRI cross-linkage. We investigated the effects of various interleukins (ILs) on expression of CD203c on blood basophils using an antibody against CD203c and flow cytometry. Of all cytokines tested, only IL-3 was found to upregulate expression of CD203c on basophils above baseline levels. The effects of IL-3 were dose- and time-dependent (EC(50): 0.1-1 ng/ml) without differences observed between healthy and allergic donors. Whereas anti-IgE induced maximum upregulation of CD203c within 15 minutes, the IL-3-induced upregulation showed a maximum after 180 minutes. IgE-receptor cross-linking resulted in enhanced expression of both CD63 and CD203c, whereas IL-3 enhanced the levels of CD203c without promoting expression of CD63. The IL-3-induced upregulation of CD203c was also observed in highly enriched basophils and was counteracted by a blocking antibody against the alpha chain of the IL-3 receptor (CD123). The IL-3-induced upregulation of CD203c was also found to depend on the presence of calcium. To analyze signaling pathways involved in IL-3-induced upregulation of CD203c, pharmacologic inhibitors were applied. The PI3-kinase inhibitors, wortmannin and LY294002 counteracted the IL-3-induced expression of CD203c, whereas MEK- and PKC inhibitors showed no effects. In conclusion, IL-3 upregulates expression of CD203c on basophils through a specific receptor and via a PI3-kinase-dependent signaling-pathway. Compared to FcepsilonRI-mediated cell activation, IL-3-induced upregulation of CD203c is a late(r) event and is not accompanied by upregulation of CD63.