Title: Omalizumab Inhibits FcεRI-mediated Activation of Human Mast Cells by Removing Surface IgE
Abstract: RATIONALE: IgE bound to the high affinity Fc epsilon receptor (FcεRI) stabilizes FcεRI expression and modulates IgE-dependent production of mediators by human mast cells. Omalizumab is a recombinant human monoclonal anti-IgE antibody that prevents IgE binding to FcεRI. We investigated the effects of omalizumab on IgE-mediated responses in human mast cells. METHODS: LAD2 and CD34+-derived human mast cell degranulation was determined by measuring the release of the granular enzyme, β-hexosaminidase. FcεRI expression was measured by quantitative (qPCR) and flow cytometry. Mast cell production of cysteinyl leukotrienes (CysLT) was measured by ELISA. IgE binding to FcεRI was measured by flow cytometry. RESULTS: Omalizumab (10 ug/mL) inhibited IgE binding to LAD2 cells by 75% compared to untreated control. Omalizumab (10 ug/mL) further blocked IgE-dependent upregulation of FcεRI expression by 90%. In addition, omalizumab removed FcεRI-bound IgE in a time-dependent manner; an effect that was detected as early as 24 hrs after addition of omalizumab resulting in a concomitant decrease in IgE-dependent FcεRI expression. Omalizumab attenuated FcεRI-dependent degranulation in a dose dependent manner. Furthermore, 100 ug/ml omalizumab prevented CysLT production. CONCLUSIONS: Omalizumab inhibits IgE and IgE/anti-IgE dependent degranulation and receptor expression by human mast cells. Furthermore, omalizumab is able to remove pre-bound IgE from sensitized mast cells thereby reducing their response to FcεRI-dependent signals. This data suggests that omalizumab is an effective inhibitor of both sensitized and unsensitized human mast cells.
Publication Year: 2010
Publication Date: 2010-02-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot