BACKGROUND: Clinical studies in kidney and liver transplantation have suggested that poor early function is associated with increased graft loss due to rejection. Ischemia-reperfusion injury may contribute to rejection by enhancing graft immunogenicity. METHODS: A rat model of unilateral in situ pulmonary ischemia-reperfusion was used to examine class II major histocompatibility complex (MHC) antigen expression. The effects of deflation during ischemia (which augments subsequent injury) as well as concurrent allostimulation were also examined. Major histocompatibility complex expression was examined 9 days after ischemia using the binding of radiolabeled anti-class II antibody and immunohistochemistry. RESULTS: Four hours of ischemia in full inflation or 2 hours of atelectatic ischemia both led to severe lung injury. Ischemia-reperfusion injury led to greater MHC expression in the ischemic lung compared with the nonischemic side. Allostimulation with mononuclear cells did not increase MHC expression in the nonischemic lung but did enhance the increase found in the ischemic lung. This was not due to a graft-versus-host response because allostimulation with F1 cells also led to a significant increase. CONCLUSIONS: Severe ischemic lung injury leads to significant increases in MHC expression, detectable after 9 days of reperfusion. Deflation during ischemia, which augments lung injury, also augments increased MHC expression. Concurrent allostimulation with foreign mononuclear cells appears to potentiate increased MHC expression after ischemia. Increases in graft MHC expression may enhance immunogenicity and increase the rejection response.
BACKGROUND: Clinical studies in kidney and liver transplantation have suggested that poor early function is associated with increased graft loss due to rejection. Ischemia-reperfusion injury may contribute to rejection by enhancing graft immunogenicity. METHODS: A rat model of unilateral in situ pulmonary ischemia-reperfusion was used to examine class II major histocompatibility complex (MHC) antigen expression. The effects of deflation during ischemia (which augments subsequent injury) as well as concurrent allostimulation were also examined. Major histocompatibility complex expression was examined 9 days after ischemia using the binding of radiolabeled anti-class II antibody and immunohistochemistry. RESULTS: Four hours of ischemia in full inflation or 2 hours of atelectatic ischemia both led to severe lung injury. Ischemia-reperfusion injury led to greater MHC expression in the ischemic lung compared with the nonischemic side. Allostimulation with mononuclear cells did not increase MHC expression in the nonischemic lung but did enhance the increase found in the ischemic lung. This was not due to a graft-versus-host response because allostimulation with F1 cells also led to a significant increase. CONCLUSIONS: Severe ischemic lung injury leads to significant increases in MHC expression, detectable after 9 days of reperfusion. Deflation during ischemia, which augments lung injury, also augments increased MHC expression. Concurrent allostimulation with foreign mononuclear cells appears to potentiate increased MHC expression after ischemia. Increases in graft MHC expression may enhance immunogenicity and increase the rejection response.
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