Chemokines in the limbal form of vernal keratoconjunctivitis.
OBJECTIVE
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.
Abu El-Asrar
A M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Struyf
S
S
Al-Kharashi
S A
SA
Missotten
L
L
Van Damme
J
J
Geboes
K
K
D000293:Adolescent; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC; D002648:Child; D003228:Conjunctiva / Q000378:metabolism; D003233:Conjunctivitis, Allergic / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism
C515456:CCL11 protein, human; C515450:CCL7 protein, human; C515453:CCL8 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins