Alcohol Ingestion by Donors Amplifies Experimental Airway Disease after Heterotopic Transplantation
American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 1161-1168, (2007)

Obliterative bronchiolitis (OB) after lung transplantation is triggered by alloimmunity, but is ultimately mediated by transforming growth factor (TGF)-₁–dependent airway fibrosis.

Chronic alcohol use increases TGF-₁ expression and renders the lung susceptible to injury. Therefore, we hypothesized that donor alcohol abuse could prime the lung allograft for OB, as many organ donors have a history of alcohol abuse.

Although donor alcohol ingestion did not increase the number of antigen-presenting cells or infiltrating lymphocytes, it nevertheless increased allograft lumenal collagen content fourfold compared with allografts from control donors. In parallel, alcohol increased TGF-₁ and -smooth muscle actin expression in allografts. Alcohol amplified airway disease even in isografts with minor alloimmune mismatches. In contrast, it did not cause any airway disease in isografts in a pure isogenic background, suggesting that a minimal alloimmune response is necessary to trigger alcohol-induced airway fibrosis.

Although alloimmune inflammation is required to initiate airway disease, alcohol primes the allograft for greater TGF-₁ expression, myofibroblast transdifferentiation, and fibrosis than by alloimmune inflammation alone. T

This has serious clinical implications, as many lung donors have underlying alcohol abuse that may prime the allograft recipient for subsequent OB.

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