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H. Alizadeh, S. Neelam, M. Hurt, J.Y. Niederkorn; Role of activated macrophages in Acanthamoeba keratitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4641.
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Purpose: In situ depletion of conjunctival macrophages with liposomes containing the macrophagicidal drug dichloromethylene diphosphonate (clodronate) profoundly exacerbated the severity, chronicity, and incidence of Acanthamoeba keratitis in Chinese hamsters. The incidence of infection in normal animals was approximately 60%, but rose to 100% on day 4 in animals treated with clodronate. These results indicate that macrophages act as a first line of defense and eliminate the Acanthamoeba trophozoites early in the infection process. The purpose of this study was to determine whether activating the conjunctival macrophage would affect the course of the disease in the Chinese hamster model of Acanthamoeba keratitis.Methods: Chinese hamster spleen cells were stimulated with concanvalin A (Con A) and the supernatants were collected 24 hours later. The supernatants were loaded into liposomes, which were fed to peritoneal macrophages in vitro. Macrophage activation was assessed by testing for the production of nitric oxide (NO) using Griess reagents. Conjunctival macrophages were activated in situ by repeated subconjunctival injection of liposomes containing Con A activated spleen cell culture supernatants. Control liposomes were loaded with bovine serum albumin (BSA).Results: Macrophages exposed to supernatants from Con A stimulated spleen cells produced 4 fold higher amounts of NO than unstimulated macrophages. Activation of macrophages via subconjunctival injection of liposomes containing supernatants from Con A stimulated spleen cell cultures resulted in rapid resolution of the corneal infection. Approximately 80% of normal animals still demonstrated evidence of corneal disease at day 14 compared to 10% incidence of infection in the Con A treated group. Moreover, at all time points examined the clinical appearance of the keratitis in animals treated with liposomes containing Con A supernatants was much less than the group treated with liposomes containing BSA (P<0.05).Conclusions: The profound mitigation of Acanthamoeba keratitis, combined with rapid clearing of infection when macrophages are activated, strongly suggest that macrophages play an important role in combating Acanthamoeba infections in the cornea.
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