2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2006111261v1 ASN.2006111261v2 18/11/2929    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Izawa, A. Articles by Abdi, R. Search for Related Content PubMed PubMed Citation Articles by Izawa, A. Articles by Abdi, R.

Importance of Donor- and Recipient-Derived Selectins in Cardiac Allograft Rejection

Atsushi Izawa^*,, Takuya Ueno, Mollie Jurewicz^*, Toshiro Ito, Katsunori Tanaka^*, Masafumi Takahashi, Uichi Ikeda, Olga Sobolev, Paolo Fiorina^*, Rex Neal Smith, Richard O. Hynes and Reza Abdi^*,

^* Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital; and Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; and Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Japan

Correspondence: Dr. Reza Abdi, Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Avenue, 3rd Floor, Boston, MA 02115. Phone: 617-732-7253; Fax: 617-732-5254; E-mail: rabdi{at}rics.bwh.harvard.edu

Received for publication November 21, 2006. Accepted for publication June 18, 2007.

The selectins expressed on activated endothelial cells (E- and P-selectin), leukocytes (L-selectin), and platelets (P-selectin) play crucial roles in the rolling and tethering of leukocytes. We explored the importance of donor and recipient selectins in acute and chronic cardiac allograft rejection using mice deficient in all three selectins (ELP^–/–). In BALB/c recipients, survival of fully allomismatched hearts from ELP^–/– C57BL/6 donors was almost double that of wild-type grafts. In ELP^–/– cardiac allografts, mononuclear cell infiltration and vasculitis of intramyocardial coronary arteries were significantly reduced. Interestingly, ELP^–/– grafts were rejected similarly in both the presence and the absence of recipient selectins, and both wild-type and ELP^–/– recipients promptly rejected wild-type hearts. Alternative adhesive molecules such as 47 integrin may compensate for the lack of selectins and may mediate rejection in ELP^–/– recipients. Chronic rejection was evaluated in a major histocompatibility complex (MHC) class II mismatch model using C57BL/6.C-H2^bm12 mice. While lack of selectins in recipients did not offer protection against chronic rejection, luminal stenosis of coronary arteries in ELP^–/– grafts was markedly diminished. In conclusion, donor-derived selectins contribute to the development of both acute and chronic cardiac allograft rejection, and targeting donor selectins may open novel therapeutic approaches in clinical transplantation.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673