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ENDOTHELIAL CELLS CONTRIBUTE TO INFLAMMATION AND FIBROSIS IN BLEOMYCIN INDUCED LUNG INJURY
Author(s) -
Leach Heather Gail,
Chrobak Izabela,
Trojanowska Maria
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.254.6
Subject(s) - bleomycin , selectin , inflammation , fibrosis , chemokine , cell adhesion molecule , cxcl1 , cd31 , pathology , biology , immunology , chemistry , microbiology and biotechnology , medicine , immunohistochemistry , chemotherapy
In this study we aimed to identify the contribution of endothelial cells (ECs) to inflammation and fibrosis induced by bleomycin lung injury. C57Bl/6 mice were injected daily with Sub‐Q bleomycin. Lungs were harvested after 14 or 28 days for analysis of total tissue by staining or FACS anaysis. ECs were isolated at day 28 by expression of surface markers (CD31+CD45−) and RNA was collected for qPCR analysis, results were confirmed by IHC. Analysis of total tissue showed an increase in macrophages by tissue staining of the Mac3 antigen and FACS analysis of CD11b+ CD11c‐ cells. In sorted ECs, expression of adhesion molecules showed up‐regulation in E‐Selectin (1.7 fold), P‐Selectin (2.4 fold, p=0.05) and CD34 (2.3 fold, p=0.01) mRNA levels. Chemokine mRNA expression was also increased in CCL2/MCP1 (2.8 fold, p=0.004), CXCL1 (1.6 fold) and CXCL2 (3.5 fold, p=0.002). Profibrotic molecules were altered, showing increases in CTGF (1.6 fold, p=0.03), PAI‐1 (3.3 fold, p=0.02), fibronectin (2.8 fold, p=0.03) and FSP1 (10.2 fold, p=0.04). Expression of selectins and chemokines suggests that EC activation plays an integral role in homing of macrophages, contributing to tissue injury after bleomycin. Further expression of pro‐fibrotic mediators in endothelial cells contributes to a sustained pro‐fibrotic environment. These results suggest that ECs play an active role in inflammation and fibrosis after bleomycin injury.