Monocyte chemoattractant peptide-1 expression during cutaneous allergic reactions in mice is mast cell dependent and largely mediates the monocyte recruitment response.

BACKGROUND

Macrophages and infiltrating monocytes comprise the largest population of cells within the airways of patients with allergic asthma. Both become activated and thus contribute to the pathologic features of allergic reactions, but the mechanism by which they are recruited has not been well documented.

OBJECTIVE

Our purpose was to assess the role of the CC chemokine monocyte chemotactic peptide-1 (MCP-1) in monocyte recruitment during allergic reactions in mice.

METHOD

We used immunohistochemistry and Northern blotting to assess MCP-1 expression, selective mast cell reconstitution of mast cell-deficient W/W(v) mice to demonstrate the mast cell dependence of MCP-1 expression and monocyte recruitment and neutralizing anti-MCP-1 antibodies to block monocyte recruitment during cutaneous allergic reactions.

RESULTS

MCP-1 was expressed largely by resident dermal cells within the allergic lesions at 4 hours after challenge, followed within several hours by an influx of monocytes; at 10 hours after challenge monocytes comprised a substantial proportion of the infiltrating cells at the nidus of the response. Mast cell-reconstituted, but not mast cell-deficient W/W(v) mice expressed MCP-1 transcripts and developed monocyte infiltrates after allergen challenge. Finally, anti-MCP-1 antibody treatments reduced by approximately 63% the influx of monocytes into the reaction sites.

CONCLUSIONS

These data clearly demonstrate the mast cell dependence of the MCP-1 expression and the monocyte influx and establish a substantial, but not exclusive, causal relationship between these 2 events.