Importance of donor-and recipient-derived selectins in cardiac allograft rejection

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...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2007-11, Vol.18 (11), p.2929-2936
Main Authors: IZAWA, Atsushi, UENO, Takuya, HYNES, Richard O, ABDI, Reza, JUREWICZ, Mollie, ITO, Toshiro, TANAKA, Katsunori, TAKAHASHI, Masafumi, IKEDA, Uichi, SOBOLEV, Olga, FIORINA, Paolo, NEAL SMITH, Rex
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Adhesion Molecules - physiology
Coronary Stenosis - etiology
Graft Rejection - etiology
Graft Survival - physiology
Heart Transplantation - adverse effects
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nephrology. Urinary tract diseases
Selectins - physiology
Tissue Donors
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Summary: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 alpha4beta7 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.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2006111261