THE KINETICS OF ALLERGEN-INDUCED TRANSCRIPTION OF MESSENGER-RNA FOR MONOCYTE CHEMOTACTIC PROTEIN-3 AND RANTES IN THE SKIN OF HUMAN ATOPIC SUBJECTS - RELATIONSHIP TO EOSINOPHIL, T-CELL, AND MACROPHAGE RECRUITMENT

The C-C chemokines RANTES and monocyte chemotactic protein-3 (MCP-3) a re potent chemoattractants in vitro for eosinophils and other cell typ es associated with allergic reactions. We tested the hypothesis that t he allergen-induced infiltration of eosinophils, T cells, and macropha ges in the skin of atopic subjects is accompanied by the appearance of mRNA(+) cells for RANTES and MCP-3. Cryostat sections were obtained f rom skin biopsies from six subjects 6, 24, and 48 h after allergen cha llenge. Tissue was processed for immunocytochemistry (ICC) and for in situ hybridization using S-35-labeled riboprobes for RANTES and MCP-3. In contrast to diluent controls, allergen provoked a significant incr ease in mRNA(+) cells for MCP-3, which peaked at 6 h and progressively declined at 24 and 48 h. This paralleled the kinetics of total (major basic protein positive [MBP](+)) and activated (cleaved form of eosin ophil cationic protein [EG2](+)) eosinophil infiltration. The allergen -induced expression of cells mRNA(+) for RANTES was also clearly demon strable at 6 h. However, the numbers were maximal at 24 h and declined slightly at the 48-h time point. The number of mRNA(+) cells for RANT ES paralleled the kinetics of infiltration of CD3(+), CD4(+), and CD8( +) T cells whereas the number of CD68(+) macrophages was still increas ing at 48 h. These data support the view that MCP-3 is involved in the regulation of the early eosinophil response to specific allergen, whe reas RANTES may have more relevance to the later accumulation of T cel ls and macrophages.