Pre-operative Determination of an Individual's Neutrophil Response: A Potential Predictor of Early Cardiac Transplant Cellular Rejection

Background: Success of heart transplantation is affected by allograft rejection, which is known as a lymphocyte-mediated process. Recent studies suggest that neutrophils contribute to this process. We hypothesized that the severity of cardiac rejection can be predicted by evaluating an individual''s neutrophil transendothelial migration potential, which can be assessed through artificial stimulation of neutrophils. Methods: Eleven patients were recruited from the active heart transplant list. Pre-operative blood samples were stained with neutrophil adhesion molecule (CD11b, CD62L, and PSGL-1) antibodies before and after in vitro stimulation with phorbol 12-myristate 13-acetate (PMA; 1 ng/ml) and lipopolysaccharide (LPS 1 μg/ml), and assessed using flow cytometry. Stimulated neutrophil responses were correlated with rejection grade of the first endomyocardial biopsy sampled 10 days post-operatively. Results: Neutrophil adhesion molecules are upregulated after artificial stimulation. Pre-operative neutrophil surface CD11b expression after in vitro lipopolysaccharide stimulation correlated with rejection grade detected in the first endomyocardial biopsy sample (R = 0.677; p = 0.022). Conclusion: Pre-operative neutrophil response to in vitro stimuli predicted the rejection grade in the first post-transplant endomyocardial biopsy specimen, suggesting that neutrophils may contribute more to cardiac allograft rejection than previously thought. [Copyright &y& Elsevier]