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The Journal of Immunology, Vol 147, Issue 7 2116-2121, Copyright © 1991 by American Association of Immunologists
ARTICLES |
BL Blaylock, Y Kouchi, CE Comment, E Corsini, GJ Rosenthal and MI Luster
Immunotoxicology Group, National Institute of Environment Health Sciences, Research Triangle Park, NC 27709.
The mechanism of action of pentamidine isethionate, a diamidino compound used in the treatment of Pneumocystis carinii pneumonia, is unknown. We recently reported that this drug may inhibit the release of inflammatory mediators from alveolar macrophages, which may be associated with its antiparasite activity. As a potential anti- inflammatory agent, we report that topically applied pentamidine reduces ear swelling in the contact hypersensitivity reaction to oxazolone in B6C3F1 mice. The application of pentamidine must occur within 1 h, at the challenge site, to be effective. Topical application appears necessary, because i.v. injection had no effect on reduction of ear swelling. In dose-response studies, a 50% reduction in ear swelling was achieved with as little as 20 micrograms of pentamidine. Pentamidine did not affect Ag transport from the challenge site to the draining lymph nodes, as measured by FITC transport. However, there was a 30 to 40% reduction in epidermal cells expressing Ia Ag from pentamidine-treated mouse ears, compared with control. Ia expression is almost exclusively limited to Langerhans cells in the normal epidermis. This reduction in Ia expression was not due to simple depletion of Langerhans cells by pentamidine, because CD45 expression was unaffected. Concurrent with reduced Ia expression, Ag presentation by pentamidine-treated Langerhans cells was also reduced. Taken together, a mechanism of action for pentamidine in inhibition of the contact hypersensitivity reaction appears to be via a reduction in Ag presentation by decreasing Ia+ Langerhans cells.
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T. E. Lawrence, L. L. Millecchia, and J. S. Fedan Fluticasone Propionate and Pentamidine Isethionate Reduce Airway Hyperreactivity, Pulmonary Eosinophilia and Pulmonary Dendritic Cell Response in a Guinea Pig Model of Asthma J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 222 - 227. [Abstract] [Full Text] |
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