HLA class I antibody-mediated endothelial and smooth muscle cell activation.
OBJECTIVE
Advances in immunosuppression and patient management have successfully improved 1-year transplant outcome. Unfortunately, antibody-mediated rejection is a major barrier to long-term graft survival. This study summarizes the effects of antibodies on endothelial cell and smooth muscle cell (SMC) migration, proliferation and leukocyte recruitment, emphasizing the intracellular signaling pathways that orchestrate these distinct functional outcomes.


RESULTS
Several studies have provided further insight into the effects of human leukocyte antigen (HLA) class I antibodies on vascular cells. We found that HLA I molecules partner with integrin β4 to transduce proliferative signaling, and identified proteins that associate with the cytoskeleton after HLA class I crosslinking. Natural killer cells have been strongly implicated in a murine model of donor-specific major histocompatibility complex I antibody-triggered neointimal thickening. A recently developed human arterial graft model revealed the role of matrix metalloproteinases in SMC mitogenesis by HLA class I antibodies. Using a donor transgenic for HLA-A2, Fukami et al. investigated the mechanisms of accommodation induced by low titers of HLA class I antibodies.


CONCLUSIONS
Ligation of HLA class I molecules with antibodies leads to the activation of intracellular signals in endothelial cells and SMCs, which in turn promote actin cytoskeletal remodeling, survival, proliferation, and recruitment of leukocytes.
Department of Pathology, UCLA Immunogenetics Center, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Xiaohai
X
Zhang
Nicole M
NM
Valenzuela
Elaine F
EF
Reed
D000199:Actins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte; D003599:Cytoskeleton / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D039663:Integrin beta4 / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D015398:Signal Transduction
D000199:Actins; D000906:Antibodies; D006680:HLA Antigens; D039663:Integrin beta4