Abstract
To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.
Highlights
Bradykinin is regarded as a substrate of the CD26/DPP-4 enzyme[1]
Rats were randomized into four groups (n=15 per group): control (CON), sham operated (Sham), LPD, and LPD + AB192 groups
The main findings from these studies are: 1) inhibition of CD26/DPP IV ameliorated PGD in the rat LTx model, protecting against ischaemia–reperfusion injury; 2) mild inflammation in the AB192 group; 3)expression of bradykinin was down-regulated with AB192 treatment, with sustained suppression of inflammation in the recipients; 4) decreased protein levels might be beneficial to attenuate the I/R injury after LTx; and 5) proper application of bradykinin may enhanced protective effects against I/R injury during transplantation
Summary
Research has revealed that bradykinin B2 receptor (B2R) antagonists play a protective role against ischemia/reperfusion (I/R) injury, in transplantation[2,3,4,5], but the significance of bradykinin in IR and the relationship between bradykinin and CD26/DPP-4 are not completely understood. It is accepted that the kallikrein-kinin system expresses potent biological activities through its final product, bradykinin[6], and that bradykinin acts via two receptor subtypes. The bradykinin B1 receptor (B1R) is up-regulated under inflammatory conditions, whereas B2R is constitutively expressed[7]. Identifying the bradykinin receptor subtypes involved at different stages during inflammation of the lung is crucial to improve our understanding of complex pulmonary conditions, including treatment (Tx)-induced lung I/R injury
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