Daniel Abraha

University of California, Los Angeles, Los Angeles, CA, United States

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Publications (2)13.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Racemic formoterol is an equimolar mixture of (R,R)- and (S,S)-formoterol. Several studies have shown (S,S)-formoterol to have proinflammatory effects. We previously reported that (S)-albuterol increased the secretion of histamine and interleukin (IL)-4 in murine mast cells. We thus hypothesized that (S,S)-formoterol promotes asthma by enhancing IL-4 production in mast cells of the asthmatic airway. Murine and human mast cells were stimulated by high affinity IgE receptor (Fc epsilon RI) cross-linking or with phorbol myristate acetate/calcium ionophore A23187 (PMA/A23187). Jurkat T cells were stimulated with PMA. Cells were pretreated with either (R,R)- or (S,S)-formoterol. Ovalbumin (OVA)-sensitized BALB/c mice were pretreated with (R,R)- or (S,S)-formoterol before each intranasal OVA challenge for 10 days. Bronchoalveolar lavage fluid was obtained from the mice. The levels of IL-4, histamine and PGD(2) were measured. Early and late allergic responses (EAR and LAR, respectively) to OVA challenge and airway hyperresponsiveness (AHR) were measured. (S,S)-formoterol enhanced the production of IL-4, histamine, and PGD(2) in mast cells, whereas (R,R)-formoterol had no effect. Neither (S,S)- nor (R,R)-formoterol had effect on IL-4 production in Jurkat T cells. In OVA-challenged mice, (S,S)-formoterol increased IL-4 secretion, whereas (R,R)-formoterol had no effect. Finally, (S,S)-formoterol enhanced the inflammatory changes in the peribronchial and perivascular areas without affecting EAR, LAR or AHR, whereas (R,R)-formoterol reduced EAR, LAR and AHR as well as cellular infiltration in the lung tissue of these mice. (S,S)-formoterol may exert adverse effects in asthma control by activating mast cells to produce proinflammatory mediators such as IL-4.
    International Archives of Allergy and Immunology 05/2004; 133(4):380-8. · 2.43 Impact Factor
  • Journal of Allergy and Clinical Immunology 09/2001; 108(2):212-4. · 11.25 Impact Factor