May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
HSV Infection and HSV-Immune Complex Both Trigger Production of Neutrophil Activating Molecules (IL-8,GRO- and GM-CSF) in Ocular Mucosal Cells
Author Affiliations & Notes
  • K. Hayashi
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • L. C. Hooper
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • B. Detrick
    Department of Pathology, Johns Hopkins University, Baltimore, Maryland
  • J. J. Hooks
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  K. Hayashi, None; L.C. Hooper, None; B. Detrick, None; J.J. Hooks, None.
  • Footnotes
    Support  Intramural Research Program of the NEI
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 492. doi:https://doi.org/
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    • Get Citation

      K. Hayashi, L. C. Hooper, B. Detrick, J. J. Hooks; HSV Infection and HSV-Immune Complex Both Trigger Production of Neutrophil Activating Molecules (IL-8,GRO- and GM-CSF) in Ocular Mucosal Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):492. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Herpetic stromal keratitis is characterized by an inflammatory infiltrate that leads to deteriorating vision even after active viral replication has subsided. Since neutrophils are a major component of this infiltrate we investigated the production of the neutrophil attractants, IL-8 and GRO-α together with GM-CSF, a functional activator and migration inhibitor of neutrophils.

Methods: : Corneal (HCE) and conjunctival epithelial cells (HCjE), primary corneal (HCRF) and conjunctival fibroblasts (HCjF) and THP-1 cells (macrophages) were infected with HSV-1 (Mckrae strain), transfected with HSV-DNA or treated with HSV-IgG (IC). After 8-24 hours incubation, supernatants were harvested and tested for the presence of IL-8, GRO-α and GM-CSF by ELISA.

Results: : Active HSV infection of HCE induced the production of GRO-α (1,600pg/ml), IL- 8 (800pg/ml) and GM-CSF (85pg/ml) by 30, 24, and 28 fold above control levels, respectively. Release of these factors was not seen with active infection of HCjE. Constitutive levels of GRO-α (1,800pg/ml) and IL-8 (1,050pg/ml) in HCRF were not increased after HSV infection. The presence of non-replicating UV inactivated and IgG complexed virus may contribute development of HSK. These two forms of inactivated HSV triggered a 10-110 fold induction of GRO-α and IL-8 in HCE and HCjE. In contrast, these inactivated forms of HSV did not alter production of these molecules in HCRF and HCjF. The macrophage cell line (THP-1) released GRO-α 2-2.5 times more than the control with the HSV-IC. In contrast, when HSV-Ig-Fab complex was used to stimulate cells, induction of GRO-α was reduced to the control levels. Thus, HSV-IC may stimulate cells through the Fc receptor. Transfection with the HSV-DNA (approximately 1,000pg/ml) did not induce production of these molecules in corneal and conjunctival epithelial cells.

Conclusions: : HCE release the neutrophil attractants (IL-8 and GRO-α) and GM-CSF in response to both replicating and nonreplicating virus. This may contribute to neutrophil infiltration into the cornea during the acute phase and the development of HSK.

Keywords: herpes simplex virus • keratitis • cornea: epithelium 
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