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) are potent chemoattractants in vitro for eosinophils and other cell types associated with allergic reactions. We tested the hypothesis that the allergen-induced infiltration of eosinophils, T cells, and macrophages in the skin of atopic subjects is accompanied by the appearance of mRNA+ cells for RANTES and MCP-3. Cryostat sections were obtained from skin biopsies from six subjects 6, 24, and 48 h after allergen challenge. Tissue was processed for immunocytochemistry (ICC) and for in situ hybridization using 35S-labeled riboprobes for RANTES and MCP-3. In contrast to diluent controls, allergen provoked a significant increase 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 eosinophil cationic protein [EG2]+) eosinophil infiltration. The allergen-induced expression of cells mRNA+ for RANTES was also clearly demonstrable 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 RANTES paralleled the kinetics of infiltration of CD3+, CD4+, and CD8+ T cells whereas the number of CD68+ macrophages was still increasing at 48 h. These data support the view that MCP-3 is involved in the regulation of the early eosinophil response to specific allergen, whereas RANTES may have more relevance to the later accumulation of T cells and macrophages.
Ying
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S
Department of Allergy and Clinical Immunology, National Heart & Lung Institute, London, United Kingdom.
Taborda-Barata
L
L
Meng
Q
Q
Humbert
M
M
Kay
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D000328:Adult; D000485:Allergens; D001706:Biopsy; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D002630:Chemotactic Factors / Q000096:biosynthesis*; D016207:Cytokines; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000485:Allergens; C515450:CCL7 protein, human; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D002630:Chemotactic Factors; D016207:Cytokines; D008222:Lymphokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger