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Luckow, B.* ; Wurst, W.

Reduced intragraft mRNA expression of matrix metalloproteinases Mmp3, Mmp12, Mmp13 and Adam8 and diminished transplant arteriosclerosis in Ccr5-deficient mice.

Eur. J. Immunol. 34, 2568-2578 (2004)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Experimental and human organ transplant studies suggest an important role for chemokine (C-C-motif) receptor-5 (CCR5) in the development of acute and chronic allograft rejection. Because early transplant damage can predispose allografts to chronic dysfunction, we sought to identify potential pathophysiologic mechanisms leading to allograft damage by using wild-type and Ccr5-deficient mice as recipients of fully MHC-mismatched heart and carotid-artery allografts. Gene expression in rejecting heart allografts was analyzed 2 and 6 days after transplantation using Affymetrix GeneChips. Microarray analysis led to identification of four metalloproteinase genes [matrix metalloproteinase (Mmp)3, Mmp12, Mmp13 and a disintegrin and metalloprotease domain (Adam)8] with significantly diminished intragraft mRNA expression in Ccr5-deficient mice at day 6. Accordingly, allografts from Ccr5-deficient mice showed less tissue remodeling and hence better preservation of the myocardial architecture compared with allografts from wild-type recipients. Moreover, survival of cardiac allografts was significantly increased in Ccr5-deficient mice. Carotid artery allografts from Ccr5-deficient recipients showed better tissue preservation, and significant reduction of neointima formation and CD3+ T cell infiltration. Ccr5 appears to play an important role in transplant-associated arteriosclerosis that may involve metalloproteinase-mediated vessel wall remodeling. We conclude that early tissue remodeling may be a critical feature in the predisposition of allografts to the development of chronic dysfunction.
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Publication type Article: Journal article
Document type Scientific Article
Keywords receptors; chemokine; mice; knockout; transplantation
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 34, Issue: 9, Pages: 2568-2578 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)