Purchase this article with an account.
James Chodosh, Roger A. Astley, Mary G. Butler, Ronald C. Kennedy; Adenovirus Keratitis: A Role for Interleukin-8. Invest. Ophthalmol. Vis. Sci. 2000;41(3):783-789.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. Adenovirus type 19 (Ad19) infection of the human cornea results in a
chronic, multifocal, subepithelial keratitis. Existing evidence
suggests that early subepithelial corneal infiltrates are composed of
polymorphonuclear neutrophils. In this study, the capacity of
Ad19-infected human corneal stromal fibroblasts (HCFs) to produce
neutrophil chemotactants (chemokines) was tested.
methods. HCFs grown from human donor corneas and passaged thrice were infected
with a corneal isolate of Ad19 or mock-infected with virus-free media.
Bioactivity of the cell supernatants was tested by a neutrophil
chemotaxis assay. Supernatants were assayed by enzyme-linked
immunosorbent assay for the neutrophil chemotactants interleukin-8
(IL-8) and GRO-α. Corneal facsimiles were generated with HCFs
and collagen type I, infected with Ad19, and assayed by
results. Ad19 infection of HCFs increased neutrophil chemotaxis from a baseline
of 0.4 ± 0.7 cells/high-powered field (hpf; mock-infected) to
21.8 ± 2.3 cells/hpf (Ad19-infected). Chemotaxis was reduced by
the addition of neutralizing antibodies against IL-8 and GRO-α.
Infection of HCFs induced quantities of IL-8 protein 300- and 1000-fold
over mock-infected controls at 4 and 24 hours, respectively (33 versus
11,813 pg/mL at 4 hours, and 57 versus 76,376 pg/mL at 24 hours, P ≤ 0.001 for both). In contrast, GRO-α protein
levels were only sevenfold higher at 24 hours postinfection (118 pg/mL
in mock-infected controls versus 880 pg/mL in Ad19-infected cell
supernatants). Neither chemokine was induced by infection of an
immortalized human corneal epithelial cell line. Immunohistochemistry
of infected corneal facsimiles demonstrated IL-8 in the extracellular
matrix within 3 days after infection.
conclusions. Production of chemokines in infected tissues facilitates an early
innate immune response to infection, and in the infected corneal stroma
represents an elementary defense mechanism. Interleukin-8 may play a
role in the development of subepithelial infiltrates in adenovirus
This PDF is available to Subscribers Only