ALTERATIONS IN THE EXPRESSION OF CHEMOKINE MESSENGER-RNA LEVELS IN FIBROSIS-RESISTANT AND FIBROSIS-SENSITIVE MICE AFTER THORACIC IRRADIATION

Fibrosis, characterized Dy the accumulation of collagen, is a conseque nce of a chronic inflammatory response. The purpose of this study was to determine if the mRNA expression of the chemokines, lymphotactin (L tn), RANTES, eotaxin, macrophage inflammatory protein (MIP)-1 alpha, - 1 beta, and -2, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1), are altered during the development of r adiation-induced pneumonitis and fibrosis. Further, rue wished to dete rmine if these changes differ between two strains of mice that vary in their sensitivity to radiation fibrosis. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single d ose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridiz ed utilizing RNase protection assays. Data were quantified by phosphor imaging and results normalized to a constitutively expressed mRNA L32. 8 weeks post-irradiation most chemokines measured were elevated to va rying degrees. The degree of elevation of each chemokine was identical in both strains. This suggested that chemotactic activity for neutrop hils, macrophages, and lymphocytes were occurring during pneumonitis. By 26 weeks post-irradiation, messages encoding Ltn, RANTES, IP-10, an d MCP-1 were elevated only in fibrosis sensitive (C57BL/6) mice. In si tu hybridization demonstrated that MCP-1 and RANTES transcripts were p roduced predominantly from macrophages and lymphocytes. These studies suggest that lymphocytic recruitment and activation are key components of radiation-induced fibrosis.