Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in amurine model of allergy

PURPOSE. TO assess the anti-inflammatory modality of a soluble extracellula r form of P-selectin glycoprotein Ligand 1 (sPSGL-1) in a mouse model of oc ular allergic response. METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated i n SWR/J mice sensitized by topical application of short ragweed pollen to t he nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; an d E, sensitized animals treated with sPSGL-1 before pollen challenge. All e xperimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inf lammatory reactions and to look for evidence of eosinophil infiltration. RESULTS.,Mice sensitized and challenged with pollen developed clinical sign s consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also c orrelated with evidence of eosinophil degranulation. However, sensitized an d challenged mice concurrently treated with sPSGL-1 displayed no inflammato ry ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic la te-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions throug h the blockade of selectin-dependent leukocyte adhesion may offer novel the rapeutic strategies to modulate inflammatory responses. The potent inhibito ry effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases.