title: [The role of endothelial cells in allograft rejection].
abstract: Endothelial cells (EC) are crucially involved in allograft rejection. They are prime targets of alloreactivity but also key players in the recruitment and extravasation of immune cells. These mechanisms also become clear in allograft biopsies with antibody-mediated complement deposition on EC and associated intracapillary accumulation of immune cells. HLA molecules are the most prominent targets of alloantibodies in AB0 compatible transplantation. Clinically relevant antibodies against other antigens such as MICA (MHC class I-related chain A) or the angiotensin II Type-1 receptor could also be convincingly demonstrated. The lack of generally available diagnostic tests for such non-HLA antibodies hampers their introduction into clinical practice. Alloantibodies undoubtedly cause allograft rejection. However, our knowledge of the molecular mechanisms underlying graft dysfunction in antibody-mediated rejection (AMR) is still fragmentary. Activation of EC by anti-endothelial cell antibodies was demonstrated in several experimental systems. Recent animal studies employing immune cell deficient transplant recipients or in-vitro assays, however, failed to demonstrate an immediate response of EC upon antibody binding and complement activation. It might therefore be considered that direct antibody- or complement-mediated EC damage is not necessarily the leading event in acute AMR. Antibody- and/or complement-induced recruitment of immune cells might rather be of crucial importance at least in the early phases of AMR.
authors.affiliation: Klinisches Institut für Pathologie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Wien, Osterreich. heinz.regele@meduniwien.ac.at
authors.forename: H
authors.initials: H
authors.lastname: Regele
mesh_terms: D000818:Animals; D003167:Complement Activation; D015935:Complement C4b / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000378:metabolism; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000276:immunology; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; C099187:MHC class I-related chain A; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D015935:Complement C4b; C032261:complement C4d