Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy.
BACKGROUND: The pathogenesis of transplant vasculopathy (TV) is a multifactorial process. We hypothesized that ischemia-reperfusion injury and antibody-mediated damage contribute to the development of TV. METHODS: Human vessels were procured from nine separate donors undergoing cardiac surgery and s...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1797104509958225920 |
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| author | Goto, R Issa, F Heidt, S Taggart, D Wood, K |
| author_facet | Goto, R Issa, F Heidt, S Taggart, D Wood, K |
| author_sort | Goto, R |
| collection | OXFORD |
| description | BACKGROUND: The pathogenesis of transplant vasculopathy (TV) is a multifactorial process. We hypothesized that ischemia-reperfusion injury and antibody-mediated damage contribute to the development of TV. METHODS: Human vessels were procured from nine separate donors undergoing cardiac surgery and stored in saline solution on ice until transplantation. BALB/c Rag2IL-2Rγ mice were transplanted with a human vessel graft on day 0. Purified anti-human leukocyte antigen class I antibody (W6/32), isotype control antibody, or saline was injected into recipient mice weekly until day 42, at which point the degree of intimal expansion (IE) of vessels was assessed by histologic analysis. RESULTS: We found that a prolonged cold ischemia time (6-12 hr) alone did not induce IE. In mice that received antibody where vessels were transplanted within 6 hr of procurement, no IE was observed. By contrast, in vessels exposed to more than 6 hr cold ischemia, both W6/32 antibody (30.4%±6.9%) and isotype control antibody (39.5%±6.0%) promoted significant IE (P<0.05 vs. saline [12.4%±1.7%]). Importantly, the isotype control antibody did not cross-react with human tissue. Interestingly, the number of mouse Fc-receptor-positive cells was significantly increased in human vessels exposed to more than 6 hr cold ischemia but only in the presence of antibody (P<0.05). CONCLUSIONS: Antibody, regardless of its specificity, may promote IE in human vessels that are injured through cold ischemia via interaction with Fc-receptor-positive cells. This highlights the importance of controlling the degree of cold ischemia in clinical transplantation in an effort to reduce the risk of TV development. |
| first_indexed | 2024-03-07T06:34:45Z |
| format | Journal article |
| id | oxford-uuid:f734856b-ea69-467e-ada2-951456329587 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:34:45Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:f734856b-ea69-467e-ada2-9514563295872022-03-27T12:41:11ZIschemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f734856b-ea69-467e-ada2-951456329587EnglishSymplectic Elements at Oxford2013Goto, RIssa, FHeidt, STaggart, DWood, KBACKGROUND: The pathogenesis of transplant vasculopathy (TV) is a multifactorial process. We hypothesized that ischemia-reperfusion injury and antibody-mediated damage contribute to the development of TV. METHODS: Human vessels were procured from nine separate donors undergoing cardiac surgery and stored in saline solution on ice until transplantation. BALB/c Rag2IL-2Rγ mice were transplanted with a human vessel graft on day 0. Purified anti-human leukocyte antigen class I antibody (W6/32), isotype control antibody, or saline was injected into recipient mice weekly until day 42, at which point the degree of intimal expansion (IE) of vessels was assessed by histologic analysis. RESULTS: We found that a prolonged cold ischemia time (6-12 hr) alone did not induce IE. In mice that received antibody where vessels were transplanted within 6 hr of procurement, no IE was observed. By contrast, in vessels exposed to more than 6 hr cold ischemia, both W6/32 antibody (30.4%±6.9%) and isotype control antibody (39.5%±6.0%) promoted significant IE (P<0.05 vs. saline [12.4%±1.7%]). Importantly, the isotype control antibody did not cross-react with human tissue. Interestingly, the number of mouse Fc-receptor-positive cells was significantly increased in human vessels exposed to more than 6 hr cold ischemia but only in the presence of antibody (P<0.05). CONCLUSIONS: Antibody, regardless of its specificity, may promote IE in human vessels that are injured through cold ischemia via interaction with Fc-receptor-positive cells. This highlights the importance of controlling the degree of cold ischemia in clinical transplantation in an effort to reduce the risk of TV development. |
| spellingShingle | Goto, R Issa, F Heidt, S Taggart, D Wood, K Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title | Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title_full | Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title_fullStr | Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title_full_unstemmed | Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title_short | Ischemia-reperfusion injury accelerates human antibody-mediated transplant vasculopathy. |
| title_sort | ischemia reperfusion injury accelerates human antibody mediated transplant vasculopathy |
| work_keys_str_mv | AT gotor ischemiareperfusioninjuryaccelerateshumanantibodymediatedtransplantvasculopathy AT issaf ischemiareperfusioninjuryaccelerateshumanantibodymediatedtransplantvasculopathy AT heidts ischemiareperfusioninjuryaccelerateshumanantibodymediatedtransplantvasculopathy AT taggartd ischemiareperfusioninjuryaccelerateshumanantibodymediatedtransplantvasculopathy AT woodk ischemiareperfusioninjuryaccelerateshumanantibodymediatedtransplantvasculopathy |