Valenzuela Nicole M, Reed Elaine F
UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, 1000 Veteran Ave Room 1-520, Los Angeles, CA 90095, USA.
Curr Transplant Rep. 2015 Sep;2(3):222-232. doi: 10.1007/s40472-015-0065-6. Epub 2015 May 24.
Human leukocyte antigen (HLA)-induced signaling in endothelial and smooth muscle cells causes dramatic cytoskeletal rearrangement, increased survival, motility, proliferation, adhesion molecule and chemokine expression, and adhesion of leukocytes. These mechanisms are directly related to endothelial activation, neointimal proliferation, and intragraft accumulation of leukocytes during antibody-mediated rejection (AMR) and chronic rejection. Clustering of HLA by ligands in , such as in antigen-presenting cells at the immune synapse, triggers physiological functions analogous to HLA antibody-induced signaling in vascular cells. Emerging evidence has revealed previously unknown functions for HLA beyond antigen presentation, including association with coreceptors in to permit signal transduction, and modulation of intracellular signaling downstream of other receptors that may be relevant to HLA signaling in the graft vasculature. We discuss the literature regarding HLA-induced signaling in vascular endothelial and smooth muscle cells, as well as under endogenous biological conditions, and how such signaling relates to functional changes and pathological mechanisms during graft injury.
人类白细胞抗原（HLA）在内皮细胞和平滑肌细胞中引发的信号传导会导致显著的细胞骨架重排、存活率增加、运动性增强、增殖、黏附分子和趋化因子表达以及白细胞黏附。这些机制与抗体介导的排斥反应（AMR）和慢性排斥反应期间的内皮激活、新生内膜增殖以及移植物内白细胞积聚直接相关。在诸如免疫突触处的抗原呈递细胞中，配体使HLA聚集，触发类似于HLA抗体在血管细胞中诱导的信号传导的生理功能。新出现的证据揭示了HLA在抗原呈递之外的先前未知的功能，包括与共受体在 中的关联以允许信号转导，以及调节其他受体下游的细胞内信号传导，这些信号传导可能与移植血管系统中的HLA信号传导相关。我们讨论了有关HLA在血管内皮细胞和平滑肌细胞中以及在内源生物学条件下诱导信号传导的文献，以及这种信号传导如何与移植损伤期间的功能变化和病理机制相关。
