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, Reza Abdi

Research output: Contribution to journalArticlepeer-review

Abstract

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 α4β7 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-H2bm12 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.

Original languageEnglish
Pages (from-to)2929-2936
Number of pages8
JournalJournal of the American Society of Nephrology
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 2007

ASJC Scopus subject areas

  • Nephrology

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