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T-Cell Chemokines Interferon-Inducible Protein-10 and Monokine Induced by Interferon-Gamma Are Upregulated in Bleomycin-Induced Lung Injury*

A. Tager; A. Luster; Richard Kradin, MD
Author and Funding Information

*From the Departments of Medicine and Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Correspondence to: Richard Kradin, MD, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114



Chest. 1999;116(suppl_1):90S. doi:10.1378/chest.116.suppl_1.90S
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Extract

Intratracheal administration of bleomycin (BLM) yields an acute pneumonitis, followed by interstitial and intra-alveolar fibrosis in mice. The fibroproliferative phase of this injury is markedly diminished by depleting CD3+ cells in vivo, indicating a critical role for T lymphocytes. The CXC chemokines interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are potent chemoattractants for activated T cells. We investigated the expression of IP-10 and MIG, and the accumulation of pulmonary mononuclear leukocytes in BLM lung injury. Female C57BL/6 (H-2b) mice were treated with BLM or saline solution intratracheally, and killed at 6 h and 1 to 7 days. BAL was performed, and lungs were excised for immunohistochemical and RNA analysis. The percentage and number of CD3+ cells in the BAL of BLM-treated mice increased at 3 days, peaked at 5 days, and diminished at 7 days; there was no increase in control mice. Northern blotting of total RNA isolated from BLM-treated mice revealed that IP-10 messenger RNA (mRNA) was induced at 6 h, peaked at 3 days, and diminished at 7 days. MIG mRNA was induced at 1 day, peaked at 5 days, and diminished at 7 days; there was minimal IP-10 and MIG mRNA expression in saline solution control mice. Immunoperoxidase staining of lung sections from BLM-treated mice identified an infiltrating population of F4/80 macrophages that coexpressed IP-10. The number of IP-10+ pulmonary macrophages paralleled the expression of IP-10 and MIG mRNA in lung. We conclude that the CXC chemokines IP-10 and MIG are upregulated early in BLM-induced injury, and may promote T-cell recruitment to the inflamed lung.


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