Basophil FcɛRI histamine release parallels expression of Src-homology 2–containing inositol phosphatases in chronic idiopathic urticaria Becky M. Vonakis,

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Presentation transcript:

Basophil FcɛRI histamine release parallels expression of Src-homology 2–containing inositol phosphatases in chronic idiopathic urticaria Becky M. Vonakis, PhD, Kavitha Vasagar, MS, Scott P. Gibbons, BS, Laura Gober, MD, Patricia M. Sterba, BS, Hyeyoun Chang, BS, Sarbjit S. Saini, MD Journal of Allergy and Clinical Immunology Volume 119, Issue 2, Pages 441-448 (February 2007) DOI: 10.1016/j.jaci.2006.09.035 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Subjects with CIU have a bimodal distribution of basophil HR to an optimal dose of anti-IgE (0.1 μg/mL) compared with normal subjects. B, CIU NR had significant reductions in basophil anti-IgE dependent release compared with normal, CIU R, and cold urticaria subjects (∗P < .00001). FMLP-induced release differed significantly only between CIU NR and CIU R (∗∗P < .001). HrHRF response was tested in a smaller subset of donors (as indicated) and was not significantly different between subjects with CIU and normal subjects. C, Basophil HR was examined across a range of anti-IgE doses in normal donors and donors with CIU (∗P < .0002 CIU NR vs normal subjects and CIU R). D, HR is presented as a percent of the maximal response achieved (see Methods). Journal of Allergy and Clinical Immunology 2007 119, 441-448DOI: (10.1016/j.jaci.2006.09.035) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Expression of Syk, SHIP-1, and SHIP-2 protein in basophils from donors with CIU, donors with cold urticaria, and normal (Nor) donors. A, Representative immunoblots shows a Nor, 2 CIU R, and 2 CIU NR donors. The scanned values were normalized to the T-cell standard lysate (Std) and corrected for cell equivalents (bottom). The upper panel demonstrates the expected 72-kd band of Syk, and the middle panel the expected band of 145 kd for SHIP-1, whereas the lower panel reveals the expected 155-kd SHIP-2 protein band. B, Mean values of Syk protein expression were not different among donor types. C, Mean normalized values for expression of SHIP-1 and SHIP-2 protein. SHIP-1 expression is reduced in cold urticaria and CIU R (∗P < .05 vs normal; #P < .05 vs CIU NR). SHIP-2 expression is increased in CIU NR compared with normal subjects (∗P < 0.05) and CIU R (#P < .03). Error bars represent SEMs. Journal of Allergy and Clinical Immunology 2007 119, 441-448DOI: (10.1016/j.jaci.2006.09.035) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Expression of phosphoAkt in basophils from CIU NR, CIU R, and a normal donor. A, Basophil lysates were examined at the indicated time points after stimulation with anti-IgE (0.1-0.3 μg/mL) for the expression of phosphoAkt and Erk. B, Phosphorylated Akt (pAKT) expression normalized to ERK protein (anti-IgE 0.1 μg/mL, dashed lines; 0.3 μg/mL, solid lines). Immunoblot representative of 2 to 3 similar experiments. Journal of Allergy and Clinical Immunology 2007 119, 441-448DOI: (10.1016/j.jaci.2006.09.035) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions