Collectin-11 as a trigger of the innate immune response in renal transplantation

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When an organ is transplanted from one person to another, the disturbance of blood flow caused by the transplant procedure frequently results in inflammation. Substantial tissue damage can occur during the phase of oxygen deprivation and during the restoration of blood flow, when the kidney is exposed to harmful oxidants. The loss of healthy tissue and subsequent scarring may shorten the life of the transplant and of the patient. Complement is a set of inflammatory molecules, which we have found is easily activated during kidney transplantation. Activated complement can contribute greatly to renal transplant injury, as our past research has shown. Our current research has identified a possible trigger for this injury; originally called kidney collectin, this trigger was later renamed collectin type-11. Our exploratory studies have indicated that collectin-11 is released into kidneys after the flow of blood is interrupted. A series of biochemical steps initiated by collectin-11 then appears to halt the recovery of the transplanted organ. We need to work out how collectin-11 attaches to the cells of the kidney after release. We also need to find out how collectin-11 can transform the transplanted kidney into an inflamed organ by unleashing the complement system. It is vital to work out the detailed biochemical steps, so that we can learn how to protect the donor organ from collectin-11. What we learn from this study will help medical science to develop more accurate monitoring of the transplant - which most likely will involve a simple urine test. The findings will also help us to work out how to shield the donor organ before it is transplanted. We already have methods for coating the donor organ with protective therapies. This work can tell us if more effort should be directed towards blocking collectin-11. Given the shortage of donor organs and reliance on kidneys that have been removed after circulatory arrest, the urgency to protect these donor organs from blood-flow damage is very high. We depend on basic research to direct our efforts; here collectin-11 seems an important new target because of its proximity to the early pathway of events that trigger the inflammatory reaction. Potentially, treatment could prevent a substantial amount of damage and extend the life of the kidney transplant.