Macrophage inflammatory protein-1α and C-C chemokine receptor-1 in allergen-induced skin late-phase reactions:: relationship to macrophages, neutrophils, basophils, eosinophils and T lymphocytes

Background Macrophage inflammatory protein (MIP)-1 alpha binds to C-C chemokine receptor (CCR)-1 with high affinity. CCR-1 is expressed on neutrophils, eosinophils, monocytes, T lymphocytes and basophils; cells characteristic of atopic allergic inflammation. In vitro, MIP-1 alpha is chemotactic for monocytes, T cells and basophils and is also a potent histamine-releasing factor for basophils and mast cells. Although increased levels of MIP-1 alpha were shown in atopic allergic disorders, the kinetics of expression of these CC chemokines in vivo is largely unknown. Objective To investigate the kinetics of expression of MIP-1 alpha and receptor CCR-1 and the relationships between the expression and infiltration of inflammatory cells in allergen-induced cutaneous late-phase reactions in atopic subjects. Methods Cryostat sections, obtained from skin biopsies from 10 human atopic subjects at 6, 24, 48, 72 h and 7 days after allergen challenge, were processed for immunohistochemistry and in situ hybridization using S-35-labelled riboprobes. Results The peak expression of allergen-induced mRNA for MIP-1 alpha and CCR-1 was 6 h. This was maintained at 24 h, and gradually returned to base line at 7 days. At 6 h, the number of cells expressing MIP-1 alpha mRNA significantly correlated with elastase(+) neutrophils and BB-1(+) basophils. At 24 h, the MIP-1 alpha mRNA(+) cells significantly correlated with CD68(+) macrophages. There were significant inverse correlations between the numbers of MIP-1 alpha mRNA cells and the numbers of Tryptase(+) mast cells at 6 and 24 h after allergen challenge. Conclusion Allergen-induced cutaneous late-phase reactions in humans were associated with increased expression of MIP-1 alpha and CCR-1. This may be relevant to the infiltration of neutrophils, eosinophils, basophils and macrophages.