title: Antibody ligation of human leukocyte antigen class I molecules stimulates migration and proliferation of smooth muscle cells in a focal adhesion kinase-dependent manner.
abstract: Chronic rejection manifests as transplant vasculopathy, which is characterized by intimal thickening of the vessels of the allograft. Intimal thickening is thought to result from the migration and proliferation of vascular smooth muscle cells (SMC) in the vessel media, followed by deposition of extracellular matrix proteins. The development of post-transplantation anti-human leukocyte antigen (HLA) antibodies (Ab) is strongly correlated with the development of transplant vasculopathy and graft loss. Here we demonstrate that cross-linking of HLA class I molecules on the surface of human SMC with anti-HLA class I Ab induced cell proliferation and migration. Class I ligation also increased phosphorylation of focal adhesion kinase (FAK), Akt, and ERK1/2 in SMC. Knockdown of FAK by siRNA attenuated class I-induced phosphorylation of Akt and ERK1/2, as well as cell proliferation and migration. These results indicate that ligation of HLA class I molecules induces SMC migration and proliferation in a FAK-dependent manner, which may be important in promoting transplant vasculopathy.
authors: Immunogenetics Center, Department of Pathology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
authors: Fang
authors: F
authors: Li
authors: Xiaohai
authors: X
authors: Zhang
authors: Yi-Ping
authors: YP
authors: Jin
authors: Arend
authors: A
authors: Mulder
authors: Elaine F
authors: EF
authors: Reed
mesh_terms: D000906:Antibodies / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016377:Organ Transplantation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
chemical_list: D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3