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SA McClellan, RP Barrett, LD Hazlett; Role of Macrophages in Restricting P. aeruginosa Growth After Corneal Infection in a Susceptible Mouse Stain . Invest. Ophthalmol. Vis. Sci. 2002;43(13):940.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study the in vivo role of macrophages (MP) in controlling P. aeruginosa replication following infection of the C57BL/6 (B6) mouse cornea. Methods: MP depletion of ocular tissues was done by repeated subconjunctival injection of liposomes containing dichloromethylene diphosphonate (clodronate). Controls were injected similary with liposomes containing PBS. Depletion efficiency was evaluated histologically and bacterial CFU in infected cornea was determined by standard plate counts. DTH responsiveness was assessed by an ear-swelling assay and antibody isotype responses to bacterial antigens and cytokine production were examined by ELISA. Results: Unexpectedly, depletion of MP resulted in a more severe ocular disease outcome to P. aeruginosa infection, including endophthalmitis and severe phthisis of the clodronate-treated vs. PBS-injected eye. PMN differences, assessed by MPO assay, however were not detected between the two groups at 1 or 3 days p.i., but significant differences were seen at 5 days p.i. (P=0.0002) with greater activity in PBS vs. clodronate-treated eyes. Bacterial counts also did not differ until 5 days p.i. when PBS-treated eyes had significantly more (P=0.0023) bacteria. However, DTH was attenuated at 24 and 48 h in clodronate vs. PBS-treated groups (P=0.002 and 0.013, respectively). Significantly elevated protein levels of IL-1 beta and MIP-1 alpha were detected at 1 day p.i. in clodronate vs. PBS groups (P=0.057, 0.003, 0.031, respectively) but not at later times p.i., while MIP-2 levels were significantly increased in clodronate vs. PBS-treated eyes at 1, 3 and 5 days p.i. (P=0.03, 0.02, and 0.05, respectively). Histology, using acid phosphatase staining, confirmed the reduction in MP at 5 days p.i. in clodronate vs. PBS-treated mice and slit lamp and standard histopathology confirmed a disparate disease response after infection between the two groups. No antibody was detected by ELISA in either group of mice. Conclusion: Unexpectedly, depletion of MP before P. aeruginosa challenge increased disease severity in susceptible B6 mice. This was associated with a decrease in PMN, despite elevated levels of MIP-2 and other inflammatory cytokines. Support: NIH RO1EY02986 and P30EY04068.
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