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. 2000 Dec;84(12):1360–1366. doi: 10.1136/bjo.84.12.1360

Chemokines in the limbal form of vernal keratoconjunctivitis

A El-Asrar 1, S Struyf 1, S Al-Kharashi 1, L Missotten 1, J Van Damme 1, K Geboes 1
PMCID: PMC1723358  PMID: 11090473

Abstract

BACKGROUND/AIMS—Chemokines are a family of low molecular weight cytokines that attract and activate leucocytes. The CC chemokines act on eosinophils, basophils, monocytes, and lymphocytes, suggesting that they play an important part in allergic diseases. The aims of this study were to investigate the expression of the CC chemokines, RANTES, eotaxin, monocyte chemotactic protein (MCP) 1, MCP-2, and MCP-3 in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and to determine the cellular source of these chemokines.
METHODS—Conjunctival biopsy specimens from nine subjects with active VKC, and six control subjects were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against RANTES, eotaxin, MCP-1, MCP-2, and MCP-3. The phenotype of inflammatory cells expressing chemokines was examined by sequential double immunohistochemistry.
RESULTS—In the normal conjunctiva, superficial epithelial cells showed a constitutive, weak cytoplasmic expression of eotaxin. Few inflammatory cells in the perivascular areas expressed RANTES, MCP-1, MCP-2, and MCP-3. In VKC specimens, the epithelium showed intense cytoplasmic eotaxin staining in all cells, and cytoplasmic RANTES staining mainly in the superficial layers. Furthermore, RANTES and eotaxin were expressed on the vascular endothelium mainly in the upper substantia propria. Compared with normal controls, VKC specimens showed significantly more inflammatory cells expressing RANTES, eotaxin, MCP-1, and MCP-3 (p<0.001, 0.0028, 0.0092, and <0.001, respectively). In VKC specimens, the numbers of inflammatory cells expressing RANTES were significantly higher than the numbers of inflammatory cells expressing eotaxin, MCP-1, and MCP-2 (all p values <0.001). Colocalisation studies revealed that the majority of inflammatory cells expressing chemokines were CD68 positive monocytes/macrophages.
CONCLUSIONS—These results demonstrate an increase in the expression of RANTES, eotaxin, MCP-1, and MCP-3 in the conjunctiva of patients with VKC compared with control subjects. These data suggest a potential role for these chemokines in the pathogenesis of VKC. Antagonists of chemokine receptors may provide new therapeutic modalities in VKC.



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Figure 1  .

Figure 1  

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(1) Vernal keratoconjunctivitis control slide, treated identically, using an irrelevant monoclonal antibody showing no staining (×300).(2) Immunohistochemical staining for eotaxin of conjunctiva from a normal control subject showing weak cytoplasmic expression in the superficial epithelial layers (×500). (3) Vernal keratoconjunctivitis. Immunohistochemical staining for eotaxin showing intense cytoplasmic staining in all epithelial cells and staining on the vascular endothelium (arrows) (×500).

Figure 2  .

Figure 2  

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(4) Vernal keratoconjunctivitis. Immunohistochemical staining for RANTES showing cytoplasmic staining in epithelial cells (arrows) and staining on the vascular endothelium (arrowheads) (×500). (5) Vernal keratoconjunctivitis. Immunohistochemical staining for MCP-1 showing cytoplasmic staining in inflammatory cells (arrows) (×500). (6) Vernal keratoconjunctivitis. Double immunohistochemical staining for RANTES (blue), and CD68 (red) showing RANTES positive cells coexpressing CD68 marker (arrows) (×1200).

Selected References

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