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HLA class I molecules partner with integrin ?4 to stimulate endothelial cell proliferation and migration.


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 ?(4) subunit after the stimulation of endothelial cells with HLA-I-specific antibodies. Knockdown of integrin ?(4) 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 ?(4)-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 ?(4) subunit to stimulate the proliferation and migration of endothelial cells, which may be important in promoting transplant vasculopathy and tumor angiogenesis.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3878299 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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HLA class I molecules partner with integrin β4 to stimulate endothelial cell proliferation and migration.

Zhang Xiaohai X   Rozengurt Enrique E   Reed Elaine F EF  

Science signaling 20101123 149


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.  ...[more]

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