Antifungal and airway remodeling roles for murine monocyte chemoattractantprotein-1/CCL2 during pulmonary exposure to Asperigillus fumigatus conidia

Asperigillus fumigatus spores or conidia are quickly eliminated from the ai rways of nonsensitized individuals but persist In individuals with allergic pulmonary responsiveness to fungus, A. fumigatus-induced allergic airway d isease is characterized by persistent airway hyperreactivity, inflammation, and fibrosis. The present study explored the role of CCR2 ligands In the m urine airway response to A. fumigatus conidia, Nonsensitized and A, fumigat us-sensitized CBA/J mice received an intratracheal challenge of A, fumigatu s conidia, and pulmonary changes were analyzed at various times after conid ia, Whole lung levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), b ut neither MCP-3/CCL7 nor MCP-5/CCL12, were significantly elevated at days 3 and 7 after conidia in nonsensitized mice. MCP-1/CCL2 was significantly i ncreased in lung samples from A, fumigatus-sensitized mice at days 14 and 3 0 after a conidia challenge. Administration of anti-MCP-1/CCL2 antiserum to nonsensitized mice for 14 days after the conidia challenge attenuated the clearance of conidia and significantly increased airway hyperreactivity, eo sinophilia, and peribronchial fibrosis compared with nonsensitized mice tha t received conidia and normal serum. adenovirus-directed overexpression of MCP-1/CCL2 in A. fumigatus-sensitized mice markedly reduced the number of c onidia, airway inflammation, and airway hyperresponsiveness at day 7 after the conidia challenge in these mice. Immunoneutralization of MCP-1/CCL2 lev els in A, fumigatus-sensitized mice during days 14-30 after the conidia cha llenge did not affect the conidia burden but significantly reduced airway h yperreactivity, lung IL-4 levels, and lymphocyte recruitment into the airwa ys compared with the control group. These data suggest that MCP-1/CCL2 part icipates in the pulmonary antifungal and allergic responses to A, fumigatus conidia.