| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Cardiology,
Molecular Biology Institute, and
Dumont-University of California, Los Angeles Transplant Center, Department of Surgery and Pathology, University of California, Los Angeles, CA 90095;
Biesecker Center and Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104; and
¶
SangStat Medical Corporation, Fremont, CA 94555
Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, exhibits potent antioxidant and anti-inflammatory properties. We developed HO-1 transgenic (Tg) mice using a rat HO-1 genomic transgene under the control of the endogenous promoter. Transgene expression was demonstrated by RT-PCR in all studied tissues, and a modest HO-1 overexpression was documented by Western, ELISA, and enzyme activity assays. To assess the effect of local vs systemic HO-1 in the acute rejection response, we used Tg mice as organ donors or recipients of MHC-incompatible heart grafts. In the local HO-1 overexpression model, Tg allografts survived 10.5 ± 0.7 days (n = 10), compared with 6.5 ± 0.4 days (n = 6) for wild-type donor controls (p = 0.0001). In the systemic HO-1 overexpression model, Tg recipients maintained allografts for 26.8 ± 3.4 days (n = 10), compared with 6.3 ± 0.1 days (n = 12) in wild-type controls (p = 0.00009). Inhibition of HO activity by treatment with tin protoporphyrin blunted survival advantage in Tg mice and resulted in acute graft rejection (n = 3). Increased carboxyhemoglobin levels were consistently noted in Tg mice. Comparisons of grafts at day 4 indicated that HO-1 overexpression was inversely associated with vasculitis/inflammatory cell infiltrate in both models. Hearts transplanted into Tg recipients showed decreased CD4+ lymphocyte infiltration and diminished immune activation, as judged by CD25 expression. Thus, although local and systemic HO-1 overexpression improved allograft outcomes, systemic HO-1 led to a more robust protection and resulted in a significant blunting of host immune activation. This Tg mouse provides a valuable tool to study mechanisms by which HO-1 exerts beneficial effects in organ transplantation.
This article has been cited by other articles:
|
|
 |
|
  H. Matsushima, H. Tanaka, N. Mizumoto, and A. Takashima Identification of crassin acetate as a new immunosuppressant triggering heme oxygenase-1 expression in dendritic cells Blood, July 2, 2009; 114(1): 64 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goldberg, M. Parolini, B. Y. Chin, E. Czismadia, L. E. Otterbein, F. H. Bach, and H. Wang Toll-like receptor 4 suppression leads to islet allograft survival FASEB J, September 1, 2007; 21(11): 2840 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Orozco, M. H. Kapturczak, B. Barajas, X. Wang, M. M. Weinstein, J. Wong, J. Deshane, S. Bolisetty, Z. Shaposhnik, D. M. Shih, et al. Heme Oxygenase-1 Expression in Macrophages Plays a Beneficial Role in Atherosclerosis Circ. Res., June 22, 2007; 100(12): 1703 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Woo, M. P. Massett, T. Shishido, S. Itoh, B. Ding, C. McClain, W. Che, S. R. Vulapalli, C. Yan, and J.-i. Abe ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor {delta} (PPAR{delta}) Stimulation J. Biol. Chem., October 27, 2006; 281(43): 32164 - 32174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sacerdoti, M. Bolognesi, M. Di Pascoli, A. Gatta, J. C. McGiff, M. L. Schwartzman, and N. G. Abraham Rat mesenteric arterial dilator response to 11,12-epoxyeicosatrienoic acid is mediated by activating heme oxygenase Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1999 - H2002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Juncos, J. P. Grande, N. Murali, A. J. Croatt, L. A. Juncos, R. P. Hebbel, Z. S. Katusic, and K. A. Nath Anomalous Renal Effects of Tin Protoporphyrin in a Murine Model of Sickle Cell Disease Am. J. Pathol., July 1, 2006; 169(1): 21 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, E. Simeoni, S. Fleury, J. Dudler, E. Fiorini, L. Kappenberger, L. K. von Segesser, and G. Vassalli Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 779 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Neto, A. Nakao, H. Toyokawa, M. A. Nalesnik, A. J. Romanosky, K. Kimizuka, T. Kaizu, N. Hashimoto, O. Azhipa, D. B. Stolz, et al. Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy Am J Physiol Renal Physiol, February 1, 2006; 290(2): F324 - F334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Laxmanan, D. Datta, C. Geehan, D. M. Briscoe, and S. Pal CD40: A Mediator of Pro- and Anti-Inflammatory Signals in Renal Tubular Epithelial Cells J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2714 - 2723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chauveau, S. Remy, P. J. Royer, M. Hill, S. Tanguy-Royer, F.-X. Hubert, L. Tesson, R. Brion, G. Beriou, M. Gregoire, et al. Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression Blood, September 1, 2005; 106(5): 1694 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chen, M. H. Kapturczak, C. Wasserfall, O. Y. Glushakova, M. Campbell-Thompson, J. S. Deshane, R. Joseph, P. E. Cruz, W. W. Hauswirth, K. M. Madsen, et al. Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway PNAS, May 17, 2005; 102(20): 7251 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, S. S. Lee, W. Gao, E. Czismadia, J. McDaid, R. Ollinger, M. P. Soares, K. Yamashita, and F. H. Bach Donor Treatment With Carbon Monoxide Can Yield Islet Allograft Survival and Tolerance Diabetes, May 1, 2005; 54(5): 1400 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kawamura, K. Ishikawa, Y. Wada, S. Kimura, H. Matsumoto, T. Kohro, H. Itabe, T. Kodama, and Y. Maruyama Bilirubin From Heme Oxygenase-1 Attenuates Vascular Endothelial Activation and Dysfunction Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 155 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-O. Pae, G.-S. Oh, B.-M. Choi, S.-C. Chae, Y.-M. Kim, K.-R. Chung, and H.-T. Chung Carbon Monoxide Produced by Heme Oxygenase-1 Suppresses T Cell Proliferation via Inhibition of IL-2 Production J. Immunol., April 15, 2004; 172(8): 4744 - 4751. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
