Journal: Annals Of Allergy, Asthma & Immunology : Official Publication Of The American College Of Allergy, Asthma, & Immunology, Volume 87, Issue 5, Nov 2001
BACKGROUND Olopatadine is a clinically effective dual-action (antihistamine/mast cell stabilizer) ophthalmic antiallergic agent. We have previously demonstrated that olopatadine inhibits tumor necrosis factor alpha (TNF-alpha) release from purified human conjunctival mast cells and that supernates from stimulated mast cells upregulate intercellular adhesion molecule 1 (ICAM-1) expression on epithelial cells via TNF-alpha.
OBJECTIVE To investigate the effect of olopatadine on the TNF-alpha-mediated mast cell upregulation of ICAM-1 expression on conjunctival epithelial cells.
METHODS Human conjunctival mast cells and epithelial cells were purified (>95%) from cadaveric tissue. Conjunctival mast cells were preincubated with three doses (30, 300, or 3,000 microM) of olopatadine or buffer alone for 30 minutes followed by 90-minute challenge with anti-immunoglobulin E (10 microg/mL). The resulting supernates were incubated with conjunctival epithelial cell monolayers for 24 hours along with the following treatments: rTNF-alpha, mast cell supernate + anti-TNF-alpha, recombinant (r)TNF-alpha + anti-TNF-alpha, the three doses of olopatadine, olopatadine supernates, olopatadine supernates + rTNF-alpha. ICAM-1 expression was measured using flow cytometry.
RESULTS Anti-IgE-stimulated human conjunctival mast cell supernates upregulated human conjunctival epithelial cell ICAM-1 expression to the same extent as rTNF-alpha. ICAM-1 upregulation could be completely blocked with anti-TNF-alpha. Preincubation of conjunctival mast cells with olopatadine significantly blocked the ability of supernates to upregulate ICAM-1 on conjunctival epithelial cells. ICAM-1 expression could be restored by adding rTNF-alpha to the olopatadine-preincubated mast cell supernates.
CONCLUSIONS Olopatadine is able to significantly decrease the anti-immunoglobulin E mast cell supernate-mediated upregulation of ICAM-1 on human conjunctival epithelial cells in vitro. This seems to be mediated through an effect on a TNF-alpha-specific mechanism.