Anti-Inflammatory Effects of αv Integrin Antagonism in Acute Kidney Allograft Rejection
| Autor: | Jens Bedke, Sophie Domhan, Tjeerd P. Sijmonsma, Amir Abdollahi, Norbert Gretz, Peter E. Huber, Markus Heuser, Zoran B. Popović, Stefan Muschal, Eva Kiss, Tomislav Stojanovic, Hermann Josef Gröne, Carl-Ludwig Behnes |
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| Rok vydání: | 2007 |
| Předmět: |
Graft Rejection
Male Integrin 030230 surgery Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Cell Adhesion medicine Animals Humans Transplantation Homologous Leukocyte Rolling Organic Chemicals Cell adhesion Cell Proliferation 030304 developmental biology Inflammation 0303 health sciences Integrin alphaVbeta3 Kidney Cell adhesion molecule Macrophages Rats Inbred Strains Fibroblasts Integrin alphaV Kidney Transplantation Coculture Techniques Rats 3. Good health Mononuclear cell infiltration medicine.anatomical_structure Immunology Leukocytes Mononuclear Cancer research biology.protein Intravital microscopy Regular Articles |
| Zdroj: | The American Journal of Pathology. 171:1127-1139 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2007.070329 |
| Popis: | Integrin-mediated cell adhesion and signaling is essential to vascular development and inflammatory processes. Elevated expression of integrin alpha(v)beta(3) has been detected in ischemia-reperfusion injury and rejecting heart allografts. We thus hypothesized that the inhibition of alpha(v)-associated integrins may have potent anti-inflammatory effects in acute kidney allograft rejection. We studied the effects of a peptidomimetic antagonist of alpha(v) integrins in two rat models of renal allotransplantation, differing in degree of major histocompatibility complex mismatch. Integrin alpha(v)beta(3) was up-regulated in rejecting renal allografts. Integrin antagonist reduced the histological signs of acute rejection, the intensity of the mononuclear cell infiltration, and cell proliferation in the grafted kidneys. This could be correlated to a reduced leukocyte-endothelial interaction and an improved peritubular microcirculation observed by intravital microscopy. In vitro under laminar flow conditions, the arrest of monocytes to interleukin-1beta-activated endothelium was decreased. Furthermore, in co-culture models the proliferation and transmigration of monocytes/macrophages, endothelium, and fibroblasts induced by renal tubular epithelia was efficiently inhibited by alpha(v) integrin antagonism. These data reveal an important role of this integrin subclass in leukocyte recruitment and development and maintenance of acute rejection; blockade of alpha(v) integrins may provide a new therapeutic strategy to attenuate acute allograft rejection. |
| Databáze: | OpenAIRE |
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