[Obliterative transplant vasculopathy: pathogenesis and pathologic mechanisms].
The obliterative transplant vasculopathy is a complication in human allografts which is found not only in kidney transplants but also in other transplanted organs and then restricts the time of organ survival considerably. The obliterative vascular lesions affects predominantly the arteries of various calibre as obliterative transplant arteriopathy (OTA), seldom the venous vessels and scarcely the arterioles. Humoral and cellular immunologic mechanisms are thought to be of important significance, especially primarily humoral mediated reactions - e.g. antibody-dependent cellular cytotoxic reactions -, developing after transplantation by sensitisation of the host. The primary target cell of the immunologic reactions seems to be the vascular endothelial cell which shows cytoplasmic and nuclear swelling and hyperplastic or also necrotic changes. By activation of vascular endothelial cells an increased expression of histocompatibility antigens, especially a neo-expression of HLA-DR on endothelial cells of renal arteries, and of other antigens and functional molecules is found. The activation of vascular endothelial cells may be also of special importance for the cellular adhesion of lymphocytes and monocytes and their interactions by interleukin-1, tumor necrosis factor, lymphotoxin and interferon-gamma. Immunohistologically macrophages/monocytes and also T-lymphocytes - more frequently of CD 8- than of CD 4-phenotype - are demonstrable in the early lesions of the arterial intima. The progression of OTA comes about by the proliferation of smooth muscle cells which express platelet derived growth factor (PDGF)-receptors and are activated by growth factors and lymphokines. The increase of smooth muscle cells and of matrix, especially of collagen, elastin, proteoglycans and fibronectin, lastly leads to the obliteration of the vascular lumina and the fibrosis. Additionally foam cells of macrophage phenotype occur in hyperlipidemic patients. The mononuclear infiltrates decrease in this later stages. Thus the pathogenetic course of the resulting arterial lesions is similar to an accelerated arteriosclerotic process.
Müller-Hermelink
H K
HK
Dämmrich
J R
JR
D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology*
D006684:HLA-DR Antigens
Die obliterative Transplantatvasculopathie: Pathogenese und Pathomechanismen.