Donor MHC and adhesion molecules in transplant arteriosclerosis

Chengwei Shi, Mark W. Feinberg, Dorothy Zhang, Anand Patel, Chang U. Sim, Zhao Ming Dong, Susan M. Chapman, Jose Carlos Gutierrez-Ramos, Denisa D. Wagner, Nicholas E.S. Sibinga, Edgar Haber

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively, due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of α-actin- positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant- associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalJournal of Clinical Investigation
Volume103
Issue number4
DOIs
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Medicine(all)

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    Shi, C., Feinberg, M. W., Zhang, D., Patel, A., Sim, C. U., Dong, Z. M., Chapman, S. M., Gutierrez-Ramos, J. C., Wagner, D. D., Sibinga, N. E. S., & Haber, E. (1999). Donor MHC and adhesion molecules in transplant arteriosclerosis. Journal of Clinical Investigation, 103(4), 469-474. https://doi.org/10.1172/JCI4584