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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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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.
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.
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.
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.
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