BRONCHIAL MUCOSAL EXPRESSION OF THE GENES ENCODING CHEMOKINES RANTES AND MCP3 IN SYMPTOMATIC ATOPIC AND NONATOPIC ASTHMATICS - RELATIONSHIPTO THE EOSINOPHIL-ACTIVE CYTOKINES INTERLEUKIN (IL)-5, GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR, AND IL-3

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenet ic variant of asthma since, unlike extrinsic (atopic) asthma, patients are skin-prick test negative to common aeroallergens and have total s erum immunoglobulin E concentrations within the normal range. However both atopic and nonatopic asthma are characterized by chronic inflamma tion of the bronchial mucosa in which eosinophils are prominent and ar e believed to be associated with local tissue damage. Therefore, speci fic eosinophil chemoattractants acting in concert with factors which p rolong eosinophil survival may at least partly account for selective e osinophil recruitment to the asthmatic bronchial mucosa. The CC chemok ines RANTES and monocyte chemotactic protein 3 (MCP-3) are potent eosi nophil chemotactic factors, while the cytokines interleukin (IL)-5, gr anulocyte macrophage-colony-stimulating factor (GM-CSF), and IL-3 prol ong eosinophil survival. We have tested the hypothesis that elevated n umbers of cells expressing mRNA for RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 are present in bronchial biopsies from atopic and no natopic asthmatics compared with atopic and nonatopic nonasthmatic con trols. The technique of in situ hybridization using S-35-labeled ribop robes was employed to detect mRNA(+) bronchial mucosal cells. Compared with controls we observed significant increases in the numbers of cel ls expressing RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 (all P values < 0.001) in atopic and nonatopic asthmatics. These observati ons support the view that atopic and nonatopic asthma are associated w ith combined bronchial mucosal expression of CC chemokines (RANTES and MCP-3), together with eosinophil-active cytokines (IL-5, GM-CSF, and IL-3). These cytokines might contribute to the bronchial mucosal accum ulation of activated eosinophils in both atopic and nonatopic variants of asthma.