Culprit of graft failure after lung transplantation identified
Investigators have identified the culprit of primary graft dysfunction (PGD), the major reason for early mortality after lung transplantation. This discovery may improve the rates of graft success.
The study, led by Northwestern University Feinberg School of Medicine and Washington University School of Medicine, was reported in Science Translational Medicine on 14 Jun 2017.
PGD represents a multifactorial injury to the transplanted lung in the first hours to days after lung transplantation. It is estimated to affect 10-25% of lung transplants and carries a mortality of up to 50%. The pathogenesis of PGD remains murky, although neutrophils have been implicated. Neutrophils are a type of white blood cells that normally circulate in the blood, and they are the first cells to migrate towards the site of injury or infection. In PGD, neutrophils are recruited into the transplanted lung, triggering inflammatory responses and tissue damage. So far, the mechanism that regulates neutrophil influx into the injured lung is not fully understood.
To answer this question, Ankit Bharat, a researcher at Northwestern University Feinberg School of Medicine, and colleagues conducted a series of experiments. They found that the intravascular nonclassical monocytes (NCMs) hidden in donor lung are responsible for the harmful influx of neutrophils after transplantation. Working with allogeneic and syngeneic models, the investigators demonstrated that depletion of NCMs could reduce neutrophil influx and lung graft injury.
Further investigation identified a critical role for NCMs in the development of PGD. NCMs upregulates a signaling pathway associated the production of CXCL2 -- a key molecule that controls the recruitment of neutrophils. CXCL2 then attracts neutrophils into the lung, leading to tissue damage.
Collectively, the data suggest that NCMs may be the culprit of PGD, and that inhibiting or depleting NCMs in donor lung could reduce the risk of PGD in the recipient.
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