M.J.S. and R.A. contributed equally to this work. K.Z. (née Agassi) did this work as a thesis in partial fulfilment of the requirements for an MD degree of the Hebrew University and Hadassah Medical School, Jerusalem.
Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury1
Article first published online: 27 SEP 2005
International Journal of Experimental Pathology
Volume 86, Issue 5, pages 279–288, October 2005
How to Cite
Segel, M. J., Aqeilan, R., Zilka, K., Lorberboum-Galski, H., Wallach-Dayan, S. B., Conner, M. W., Christensen, T. G. and Breuer, R. (2005), Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury. International Journal of Experimental Pathology, 86: 279–288. doi: 10.1111/j.0959-9673.2005.00436.x
- Issue published online: 27 SEP 2005
- Article first published online: 27 SEP 2005
- Received for publication: 1 April 2004 Accepted for publication: 15 April 2005
- genetic engineering;
- interstitial lung disease
The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE664Glu, an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE664Glu. However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.