Submitted on September 8, 2008
Revised on June 1, 2009
Accepted on June 3, 2009
Erythromycin-induced CXCR4 expression on microvascular endothelial cells
Yasuyuki Takagi1, NAOZUMI HASHIMOTO1*, Sem H. Phan2, Kazuyoshi Imaizumi1, Masaki Matsuo1, Harunori Nakashima1, Izumi Hashimoto1, Yuta Hayashi1, Tsutomu Kawabe3, Kaoru Shimokata4, and Yoshinori Hasegawa1
1 NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE
2 University of Michigan
3 Nagoya University Graduate School of Health
4 Chubu University
* To whom correspondence should be addressed. E-mail: hashinao{at}med.nagoya-u.ac.jp.
Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated. In this study, we demonstrated that EM markedly induced CXCR4 surface expression on microvascular endothelial cells in vitro and lung capillary endothelial cells in vivo. This ability to induce CXCR4 surface expression on endothelial cells was restricted to 14- membered ring macrolides, and was not observed in other antibiotics including a 16-membered ring macrolide, josamycin. Furthermore, this EM-induced expression of CXCR4 on endothelial cells was functionally significant as demonstrated by chemotaxis assays in vitro. These findings suggest that EM-induced CXCR4 surface expression on endothelial cells may promote migration of CXCR4-expressing endothelial cells into sites of tissue injury, which may be associated with the known anti-inflammatory activity of this macrolide.
