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International Immunology Advance Access originally published online on October 29, 2007
International Immunology 2007 19(12):1349-1359; doi:10.1093/intimm/dxm104
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Hydrogen peroxide increases human leukocyte adhesion to porcine aortic endothelial cells via NF{kappa}B-dependent up-regulation of VCAM-1

Sukmook Lee1,2,5, Junho Chung2,4,5, In Su Ha2,5, Kyesook Yi2,5, Ji Eun Lee2, Hee Gyung Kang5, Inho Choi2,5, Kook-Hwan Oh5,6, Jae Young Kim3,5, Charles D. Surh7 and Curie Ahn2,5,6

1 Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea
2 Cancer Research Institute, Seoul National University, Seoul 110-744, Korea
3 Department of Biological Science, Gachon Medical School, Incheon 405-760, Korea
4 Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-744, Korea
5 Transplantation Research Institute, Seoul National University, Seoul 110-744, Korea
6 Department of Internal Medicine, Seoul National University Hospital, Seoul 110-799, Republic of Korea
7 Department of Immunology, IMM-26, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Correspondence to: C. Ahn; E-mail: curie{at}snu.ac.kr

Although a severe shortage of organs in transplantation can be overcome by using xenotransplantation of porcine donor organs, profound immune rejection to xenogeneic antigens remains a main obstacle. To elucidate the role of hydrogen peroxide (H2O2) on xenogeneic immune responses, we investigated its effects on porcine aortic endothelial cells (PAECs). We found that H2O2 can specifically induce vascular cell adhesion molecule-1 (VCAM-1) expression on PAECs, but little on human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs). Furthermore, we further confirmed that H2O2 induces activation of NF{kappa}B in PAECs, but not in HAECs. Interestingly, cell adhesion assay showed that U937, human promonocytic leukocyte, can adhere to PAECs in an H2O2-dependent manner and by using a neutralizing assay with anti-VCAM-1-specific antibodies, we also found that the interaction is mediated primarily by VCAM-1. Finally, we also demonstrated that up-regulation of VCAM-1 expression on PAECs by reactive oxygen species-producing HL-60, human leukemic neutrophil cells, could be significantly diminished by over-expressing an H2O2-removing catalase. In summary, our results suggest that NF{kappa}B-dependent porcine VCAM-1 expression by H2O2 may promote interaction of human leukocyte to PAECs, and thus may play an important role on inducing xenogeneic immune responses.

Keywords: endothelial cells, hydrogen peroxide, pig, vascular cell adhesion molecule, xenotransplantation

Transmitting editor: S. Hedrick

Received 24 January 2007, accepted 27 September 2007.


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