Abstract
Purpose: :
Our whole genome analysis of transcriptome of acute allergic inflammation identified monocyte chemoattractant protein-1 (MCP-1/CCL2) as presumable disease- susceptible gene (IOVS 2008 in press). Using experimental murine allergic conjunctivitis model, we evaluated the roles of MCP-1 and its receptor, CCR2.
Methods: :
The effect of CCR2 blockade was evaluated by in vitro isolated conjunctival mast cells. The role of MCP-1 in the conjunctiva was evaluated by subconjunctival injection of the recombinant MCP-1 protein into non-sensitized mice. Ragweed pollen-sensitized mice were provoked for acute allergic inflammation by the allergen instillation. Roles of MCP-1 were evaluated clinically and histologically by treatment of anti-MCP-1 antibody or specific CCR2 antagonist (RS 504393).
Results: :
In vitro study revealed CCR2 blockade significantly suppressed mast cell degranulation (P<0.05). MCP-1 injection activated mast cell degranulation in non-sensitized mice. Inhibition of MCP-1/CCR2 significantly suppressed early phase clinical symptoms and allergen-specific mast cell degranulation (P<0.05) without affect on allergen-specific IgE, or Th2 cytokine release from isolated draining lymph node cells.
Conclusions: :
MCP-1/CCR2 plays important roles in allergen-specific mast cell activation and acute phase inflammation in murine experimental allergic conjunctivitis.
Keywords: cytokines/chemokines • conjunctivitis • receptors