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Sci. Signal., 23 November 2010
Vol. 3, Issue 149, p. ra85
[DOI: 10.1126/scisignal.2001158]

RESEARCH ARTICLES

HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration

Xiaohai Zhang1, Enrique Rozengurt2, and Elaine F. Reed1*

1 Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
2 Division of Digestive Diseases, Department of Medicine, Center for Ulcer Research and Education, Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Abstract: Among transplant recipients, those who produce antibodies against the donor’s human leukocyte antigens (HLAs) are at higher risk for antibody-mediated rejection and transplant vasculopathy, which is a progressive, vasculo-occlusive disease that results in ischemic injury and deterioration of organ function. Antibodies against HLA class I (HLA-I) molecules are thought to contribute to transplant vasculopathy by triggering signals that elicit the activation and proliferation of endothelial cells. Here, we demonstrate a molecular association between HLA-I and the integrin β4 subunit after the stimulation of endothelial cells with HLA-I–specific antibodies. Knockdown of integrin β4 in these cells abrogated the ability of HLA-I to stimulate the phosphorylation of the kinases Akt, extracellular signal–regulated kinase (ERK), and Src, as well as cellular proliferation. Similarly, reducing the abundance of HLA-I suppressed integrin β4–mediated phosphorylation of ERK and the migration of endothelial cells on laminin-5, a component of the extracellular matrix. These results indicate a mutual dependency between HLA-I and the integrin β4 subunit to stimulate the proliferation and migration of endothelial cells, which may be important in promoting transplant vasculopathy and tumor angiogenesis.

* To whom correspondence should be addressed. E-mail: ereed{at}mednet.ucla.edu

Citation: X. Zhang, E. Rozengurt, E. F. Reed, HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration. Sci. Signal. 3, ra85 (2010).

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