Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (intrinsic) asthmatics

Atopic (AA) and nonatopic (NAA) asthma are characterized by chronic inflamm ation and local tissue eosinophilia, Many C-C chemokines are potent eosinop hil chemoattractants and act predominantly via the CCR3, We examined the ex pression of eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), MCP-4, and CCR3 in the bronchial mucosa from atopic (AA) and nonat opic (intrinsic; NAA) asthmatics and compared our findings with atopic (AC) and nonatopic nonasthmatic controls (NC), Cryostat sections were processed for immunohistochemistry (IHC), in situ hybridization (ISH), and double IH C/ISH, Compared with AC and NC, the numbers of EG2(+) cells and the cells e xpressing mRNA for eotaxin, eotaxin-2, RANTES, MCP-3, MCP-4, and CCR3 were significantly increased in AA and NAA (p < 0.01). Nonsignificant difference s in these variants were observed between AA and NAA and between AC and NC. Significant correlations between the cells expressing eotaxin or CCR3 and EG2(+) eosinophils in the bronchial tissue were also observed for both AA ( p < 0.01) and NAA (p = 0.01), Moreover, in the total asthmatic group (AA NAA) there was a significant inverse correlation between the expression of eotaxin and that of the histamine PC20 (p < 0.05), Sequential IHC/ISH showe d that cytokeratin(+) epithelial cells, CD31(+) endothelial cells, and CD68 (+) macrophages were the major sources of eotaxin, eotaxin-2, RANTES, MCP-3 , and MCP-4. There was no significantly different distribution of cells exp ressing mRNA for these chemokines between atopic and nonatopic asthma, Thes e findings suggest that multiple C-C chemokines, acting at least in part vi a CCR3, contribute to bronchial eosinophilia in both atopic and nonatopic a sthma.